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Wan Y, Zhang L, Wang L, Zhang Y, Gao F. High-altitude chronic hypoxia prevents myocardial dysfunction in experimental model of type 2 diabetes. Arch Biochem Biophys 2025; 768:110371. [PMID: 40086566 DOI: 10.1016/j.abb.2025.110371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 02/19/2025] [Accepted: 03/03/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND High-altitude chronic hypoxia (CHH) has a favorable impact on the lower prevalence of diabetes together with the better glucose tolerance. However, whether it prevents diabetic cardiomyopathy remains unclear. This study aimed to investigate the effects of CHH on left ventricular (LV) function in experimental model of type 2 diabetes. METHODS Sprague-Dawley rats were randomly divided into control (altitude 500 m), DM (diabetes mellitus and altitude 500 m), CHH (altitude 4250 m and non-diabetic for 2 weeks), CHH-DM2 (altitude 4250 m and DM for 2 weeks), and CHH-DM8 (altitude 4250 m and DM for 8 weeks) groups. The experimental model of type 2 diabetes was induced by a high-fat diet plus low-dose streptozotocin (35 mg/kg, intraperitoneal) after fasted overnight. Left ventricular cardiac function and global myocardial strain were evaluated at 2, and 8 weeks by 7.0 T cardiovascular magnetic resonance. Subsequently, biochemical indices, histological evaluation, and levels of hypoxia-induced factor (HIF)-1α were assessed. RESULTS Left ventricular ejection fraction (LVEF), global longitudinal (GLS), circumferential (GCS), and radial (GRS) strains significantly decreased in the DM group compared with the controls. However, these abnormalities in DM rats were significantly prevented in the CHH-DM2 group, and were further improved in CHH-DM8 group. Mechanistically, prolonged CHH at high altitude further reduced cardiac apoptosis, and oxidative stress, and increased autophagy, and the expression of HIF-1α in diabetic myocardial tissue. CONCLUSIONS CHH exerted cardioprotective effects by improving LV function, increasing myocardial strain and attenuating cardiac hypertrophy in type 2 diabetic rats, likely through reducing apoptosis and oxidative stress, activating autophagy and HIF-1α signaling in diabetic rats.
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Affiliation(s)
- Yixuan Wan
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Lisha Zhang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Lei Wang
- Molecular Imaging Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yu Zhang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - FaBao Gao
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.
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Li G, Meex RCR, Goossens GH. The role of tissue oxygenation in obesity-related cardiometabolic complications. Rev Endocr Metab Disord 2025; 26:19-30. [PMID: 39298040 PMCID: PMC11790814 DOI: 10.1007/s11154-024-09910-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/08/2024] [Indexed: 09/21/2024]
Abstract
Obesity is a complex, multifactorial, chronic disease that acts as a gateway to a range of other diseases. Evidence from recent studies suggests that changes in oxygen availability in the microenvironment of metabolic organs may exert an important role in the development of obesity-related cardiometabolic complications. In this review, we will first discuss results from observational and controlled laboratory studies that examined the relationship between reduced oxygen availability and obesity-related metabolic derangements. Next, the effects of alterations in oxygen partial pressure (pO2) in the adipose tissue, skeletal muscle and the liver microenvironment on physiological processes in these key metabolic organs will be addressed, and how this might relate to cardiometabolic complications. Since many obesity-related chronic diseases, including type 2 diabetes mellitus, cardiovascular diseases, chronic kidney disease, chronic obstructive pulmonary disease and obstructive sleep apnea, are characterized by changes in pO2 in the tissue microenvironment, a better understanding of the metabolic impact of altered tissue oxygenation can provide valuable insights into the complex interplay between environmental and biological factors involved in the pathophysiology of metabolic impairments. This may ultimately contribute to the development of novel strategies to prevent and treat obesity-related cardiometabolic diseases.
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Affiliation(s)
- Geng Li
- Department of Human Biology, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre+, PO Box 616, Maastricht, 6200 MD, The Netherlands
| | - Ruth C R Meex
- Department of Human Biology, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre+, PO Box 616, Maastricht, 6200 MD, The Netherlands
| | - Gijs H Goossens
- Department of Human Biology, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre+, PO Box 616, Maastricht, 6200 MD, The Netherlands.
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3
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Salgado RM, Ryan BJ, Seeley AD, Charkoudian N. Improving Endurance Exercise Performance at High Altitude: Traditional and Nontraditional Approaches. Exerc Sport Sci Rev 2025; 53:10-22. [PMID: 39262050 DOI: 10.1249/jes.0000000000000347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/13/2024]
Abstract
Acute exposure to terrestrial altitude (hypobaric hypoxia) causes decrements in endurance performance relative to sea level. Altitude acclimatization consistently results in partial attenuation of these decrements, but due to logistical challenges, it is not readily implemented. We discuss mechanisms and impact (or lack thereof) of other non-acclimatization interventions to improve endurance performance and provide suggestions for future research directions.
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Affiliation(s)
- Roy M Salgado
- US Army Research Institute of Environmental Medicine, Thermal and Mountain Medicine Division, Natick, MA
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Karpęcka-Gałka E, Frączek B. Nutrition, hydration and supplementation considerations for mountaineers in high-altitude conditions: a narrative review. Front Sports Act Living 2024; 6:1435494. [PMID: 39584049 PMCID: PMC11582915 DOI: 10.3389/fspor.2024.1435494] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Accepted: 10/11/2024] [Indexed: 11/26/2024] Open
Abstract
Staying and climbing in high mountains (>2,500 m) involves changes in diet due to poor access to fresh food, lack of appetite, food poisoning, environmental conditions and physiological changes. The purpose of this review is to summarize the current knowledge on the principles of nutrition, hydration and supplementation in high-altitude conditions and to propose practical recommendations/solutions based on scientific literature data. Databases such as Pubmed, Scopus, ScienceDirect and Google Scholar were searched to find studies published from 2000 to 2023 considering articles that were randomized, double-blind, placebo-controlled trials, narrative review articles, systematic reviews and meta-analyses. The manuscript provides recommendations for energy supply, dietary macronutrients and micronutrients, hydration, as well as supplementation recommendations and practical tips for mountaineers. In view of the difficulties of being in high mountains and practicing alpine climbing, as described in the review, it is important to increase athletes' awareness of nutrition and supplementation in order to improve well-being, physical performance and increase the chance of achieving a mountain goal, and to provide the appropriate dietary care necessary to educate mountaineers and personalize recommendations to the needs of the individual.
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Affiliation(s)
- Ewa Karpęcka-Gałka
- Doctoral School of Physical Culture Sciences, University of Physical Education in Krakow, Cracow, Poland
| | - Barbara Frączek
- Department of Sports Medicine and Human Nutrition, Institute of Biomedical Sciences, University of Physical Education in Krakow, Cracow, Poland
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Narang BJ, Drole K, Barber JFP, Goods PSR, Debevec T. Utility of hypoxic modalities for musculoskeletal injury rehabilitation in athletes: A narrative review of mechanisms and contemporary perspectives. J Sports Sci 2024:1-14. [PMID: 39448892 DOI: 10.1080/02640414.2024.2416779] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 10/08/2024] [Indexed: 10/26/2024]
Abstract
Recent evidence suggests that different hypoxic modalities might accelerate the rehabilitation process in injured athletes. In this review, the application of hypoxia during rehabilitation from musculoskeletal injury is explored in relation to two principles: (1) facilitating the healing of damaged tissue, and (2) mitigating detraining and inducing training adaptations with a reduced training load. Key literature that explores the underlying mechanisms for these themes is presented, and considerations for practice and future research directions are outlined. For principle (1), passive intermittent hypoxic exposures might accelerate tissue healing through angiogenic and osteogenic mechanisms. Experimental evidence is largely derived from rodent research, so further work is warranted to establish whether clinically meaningful effects can be observed in humans, before optimal protocols are determined (duration, frequency, and hypoxic severity). Regarding principle (2), a hypoxia-related increase in the cardiometabolic stimulus imposed by low-load exercise is appealing for load-compromised athletes. As rehabilitation progresses, a variety of hypoxic modalities can be implemented to enhance adaptation to energy-systems and resistance-based training, and more efficiently return the athlete to competition readiness. While hypoxic modalities seem promising for accelerating musculoskeletal injury rehabilitation in humans, and are already being widely used in practice, a significant gap remains regarding their evidence-based application.
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Affiliation(s)
- Benjamin Jonathan Narang
- Faculty of Sport, University of Ljubljana, Ljubljana, Slovenia
- Department of Automatics, Biocybernetics, and Robotics, Jožef Stefan Institute, Ljubljana, Slovenia
| | - Kristina Drole
- Faculty of Sport, University of Ljubljana, Ljubljana, Slovenia
| | | | - Paul S R Goods
- Physical Activity, Sport and Exercise (PHASE) Research Group, School of Allied Health (Exercise Science), Murdoch University, Perth, Australia
- Centre for Healthy Ageing, Health Futures Institute, Murdoch University, Perth, Australia
| | - Tadej Debevec
- Faculty of Sport, University of Ljubljana, Ljubljana, Slovenia
- Department of Automatics, Biocybernetics, and Robotics, Jožef Stefan Institute, Ljubljana, Slovenia
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Margolis LM, Wilson MA, Drummer DJ, Carrigan CT, Murphy NE, Allen JT, Dawson MA, Mantzoros CS, Young AJ, Pasiakos SM. Pioglitazone does not enhance exogenous glucose oxidation or metabolic clearance rate during aerobic exercise in men under acute high-altitude exposure. Am J Physiol Regul Integr Comp Physiol 2024; 327:R25-R34. [PMID: 38682243 PMCID: PMC11381008 DOI: 10.1152/ajpregu.00064.2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 04/09/2024] [Accepted: 04/23/2024] [Indexed: 05/01/2024]
Abstract
Insulin insensitivity decreases exogenous glucose oxidation and metabolic clearance rate (MCR) during aerobic exercise in unacclimatized lowlanders at high altitude (HA). Whether use of an oral insulin sensitizer before acute HA exposure enhances exogenous glucose oxidation is unclear. This study investigated the impact of pioglitazone (PIO) on exogenous glucose oxidation and glucose turnover compared with placebo (PLA) during aerobic exercise at HA. With the use of a randomized crossover design, native lowlanders (n = 7 males, means ± SD, age: 23 ± 6 yr, body mass: 84 ± 11 kg) consumed 145 g (1.8 g/min) of glucose while performing 80 min of steady-state (1.43 ± 0.16 V̇o2 L/min) treadmill exercise at HA (460 mmHg; [Formula: see text] 96.6 mmHg) following short-term (5 days) use of PIO (15 mg oral dose per day) or PLA (microcrystalline cellulose pill). Substrate oxidation and glucose turnover were determined using indirect calorimetry and stable isotopes ([13C]glucose and 6,6-[2H2]glucose). Exogenous glucose oxidation was not different between PIO (0.31 ± 0.03 g/min) and PLA (0.32 ± 0.09 g/min). Total carbohydrate oxidation (PIO: 1.65 ± 0.22 g/min, PLA: 1.68 ± 0.32 g/min) or fat oxidation (PIO: 0.10 ± 0.0.08 g/min, PLA: 0.09 ± 0.07 g/min) was not different between treatments. There was no treatment effect on glucose rate of appearance (PIO: 2.46 ± 0.27, PLA: 2.43 ± 0.27 mg/kg/min), disappearance (PIO: 2.19 ± 0.17, PLA: 2.20 ± 0.22 mg/kg/min), or MCR (PIO: 1.63 ± 0.37, PLA: 1.73 ± 0.40 mL/kg/min). Results from this study indicate that PIO is not an effective intervention to enhance exogenous glucose oxidation or MCR during acute HA exposure. Lack of effect with PIO suggests that the etiology of glucose metabolism dysregulation during acute HA exposure may not result from insulin resistance in peripheral tissues.NEW & NOTEWORTHY Short-term (5 days) use of the oral insulin sensitizer pioglitazone does not alter circulating glucose or insulin responses to enhance exogenous glucose oxidation during steady-state aerobic exercise in young healthy men under simulated acute (8 h) high-altitude (460 mmHg) conditions. These results indicate that dysregulations in glucose metabolism in native lowlanders sojourning at high altitude may not be due to insulin resistance at peripheral tissue.
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Affiliation(s)
- Lee M Margolis
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts, United States
| | - Marques A Wilson
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts, United States
| | - Devin J Drummer
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts, United States
- Oak Ridge Institute for Science and Education, Belcamp, Maryland, United States
| | - Christopher T Carrigan
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts, United States
| | - Nancy E Murphy
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts, United States
| | - Jillian T Allen
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts, United States
| | - M Alan Dawson
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts, United States
| | - Christos S Mantzoros
- Department of Medicine, Beth-Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States
- Department of Medicine, Veterans Affairs Boston Healthcare System, Boston, Massachusetts, United States
| | - Andrew J Young
- United States Army Research Institute of Environmental Medicine, Natick, Massachusetts, United States
- Oak Ridge Institute for Science and Education, Belcamp, Maryland, United States
| | - Stefan M Pasiakos
- Office of Dietary Supplements, National Institutes of Health, Bethesda, Maryland, United States
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Burtscher J, Raberin A, Brocherie F, Malatesta D, Manferdelli G, Citherlet T, Krumm B, Bourdillon N, Antero J, Rasica L, Burtscher M, Millet GP. Recommendations for Women in Mountain Sports and Hypoxia Training/Conditioning. Sports Med 2024; 54:795-811. [PMID: 38082199 PMCID: PMC11052836 DOI: 10.1007/s40279-023-01970-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/06/2023] [Indexed: 04/28/2024]
Abstract
The (patho-)physiological responses to hypoxia are highly heterogeneous between individuals. In this review, we focused on the roles of sex differences, which emerge as important factors in the regulation of the body's reaction to hypoxia. Several aspects should be considered for future research on hypoxia-related sex differences, particularly altitude training and clinical applications of hypoxia, as these will affect the selection of the optimal dose regarding safety and efficiency. There are several implications, but there are no practical recommendations if/how women should behave differently from men to optimise the benefits or minimise the risks of these hypoxia-related practices. Here, we evaluate the scarce scientific evidence of distinct (patho)physiological responses and adaptations to high altitude/hypoxia, biomechanical/anatomical differences in uphill/downhill locomotion, which is highly relevant for exercising in mountainous environments, and potentially differential effects of altitude training in women. Based on these factors, we derive sex-specific recommendations for mountain sports and intermittent hypoxia conditioning: (1) Although higher vulnerabilities of women to acute mountain sickness have not been unambiguously shown, sex-dependent physiological reactions to hypoxia may contribute to an increased acute mountain sickness vulnerability in some women. Adequate acclimatisation, slow ascent speed and/or preventive medication (e.g. acetazolamide) are solutions. (2) Targeted training of the respiratory musculature could be a valuable preparation for altitude training in women. (3) Sex hormones influence hypoxia responses and hormonal-cycle and/or menstrual-cycle phases therefore may be factors in acclimatisation to altitude and efficiency of altitude training. As many of the recommendations or observations of the present work remain partly speculative, we join previous calls for further quality research on female athletes in sports to be extended to the field of altitude and hypoxia.
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Affiliation(s)
- Johannes Burtscher
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland
| | - Antoine Raberin
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland
| | - Franck Brocherie
- Laboratory Sport, Expertise and Performance (EA 7370), French Institute of Sport, Paris, France
| | - Davide Malatesta
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland
| | - Giorgio Manferdelli
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland
| | - Tom Citherlet
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland
| | - Bastien Krumm
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland
| | - Nicolas Bourdillon
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland
| | - Juliana Antero
- Institut de Recherche Bio-Médicale Et d'Épidémiologie du Sport (EA 7329), French Institute of Sport, Paris, France
| | - Letizia Rasica
- Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada
| | - Martin Burtscher
- Department of Sport Science, University of Innsbruck, Innsbruck, Austria
| | - Grégoire P Millet
- Institute of Sport Sciences, Faculty of Biology and Medicine, University of Lausanne, Building Synathlon, Campus Dorigny, 1015, Lausanne, Switzerland.
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Baur DA, Baur KG, Buchanan BK, Ortiz MJ, Doody AG. Load carriage physiology in normoxia and hypoxia. Eur J Appl Physiol 2024; 124:925-943. [PMID: 37740748 PMCID: PMC10879375 DOI: 10.1007/s00421-023-05320-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Accepted: 09/08/2023] [Indexed: 09/25/2023]
Abstract
PURPOSE To determine the effects of load carriage in normoxia and normobaric hypoxia on ventilatory responses, hemodynamics, tissue oxygenation, and metabolism. METHODS Healthy males (n = 12) completed 3 randomly ordered baseline graded exercise tests in the following conditions: (1) unloaded normoxic (U: FIO2 = 20.93%), (2) loaded (~ 30 kg) normoxic (LN), and (3) loaded hypoxic simulating ~ 3650 m (LH: FIO2 = ~ 13%). Thereafter, experimental exercise trials were completed in quasi-randomized order (i.e., U completed first) consisting of 3 × 10 min of walking (separated by 5 min seated rest) with stages matched with the U condition (in ascending order) for relative intensity, absolute oxygen consumption ([VO2]; 1.7 L min-1), and walking speed (1.45 ± 0.15 m s-1). RESULTS Load carriage increased perceived exertion and reduced VO2max (LN: - 7%; LH: - 32%; p < 0.05). At matched VO2, stroke volume and tidal volume were reduced and maintained with LN and LH vs. U, respectively (p < 0.05). Increases in cardiac output and minute ventilation at matched VO2 (with LH) and speed (with LN and LH), were primarily accomplished via increases in heart rate and breathing frequency (p < 0.05). Cerebral oxygenated hemoglobin (O2HHb) was increased at all intensities with LN, but deoxygenated hemoglobin and total hemoglobin were increased with LH (p < 0.05). Muscle oxygen kinetics and substrate utilization were similar between LN and U, but LH increased CHO dependence and reduced muscle O2HHb at matched speed (p < 0.05). CONCLUSION Load carriage reduces cardiorespiratory efficiency and increases physiological strain, particularly in hypoxic environments. Potential load carriage-induced alterations in cerebral blood flow may increase the risk for altitude illnesses and requires further study.
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Affiliation(s)
- Daniel A Baur
- Department of Human Performance and Wellness, Virginia Military Institute, 208 Cormack Hall, Lexington, VA, 24450, USA.
| | - Katherine G Baur
- Department of Human Performance and Wellness, Virginia Military Institute, 208 Cormack Hall, Lexington, VA, 24450, USA
| | - Beverley K Buchanan
- Department of Human Performance and Wellness, Virginia Military Institute, 208 Cormack Hall, Lexington, VA, 24450, USA
| | - Miles J Ortiz
- Department of Human Performance and Wellness, Virginia Military Institute, 208 Cormack Hall, Lexington, VA, 24450, USA
| | - Abaigeal G Doody
- Department of Human Performance and Wellness, Virginia Military Institute, 208 Cormack Hall, Lexington, VA, 24450, USA
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Urdampilleta Otegui A, Roche Collado E. Intermittent hypoxia in sport nutrition, performance, health status and body composition. NUTR HOSP 2024; 41:224-229. [PMID: 38095103 DOI: 10.20960/nh.04692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2024] Open
Abstract
Introduction Intermittent hypoxia refers to the discontinuous use of low oxygen levels in normobaric environment. These conditions can be reproduced in hypoxic tents or chambers while the individual is training in different physical activity protocols. Intermittent hypoxia can affect several body systems, impacting nutrition, physical performance, health status and body composition. Therefore, it is necessary to assess protocols, regarding time and frequency of exposure, passive exposure or training in hypoxia, and the simulated altitude. At the molecular level, the hypoxia-inducible factor-1α is the primary factor mediating induction of target genes, including vascular endothelial growth factor and erythropoietin. The goal of these molecular changes is to preserve oxygen supply for cardiac and neuronal function. In addition, hypoxia produces a sympathetic adrenal activation that can increase the resting metabolic rate. Altogether, these changes are instrumental in protocols designed to improve physical performance as well as functional parameters for certain pathological disorders. In addition, nutrition must adapt to the increased energy expenditure. In this last context, performing physical activity in intermittent hypoxia improves insulin sensitivity by increasing the presence of the glucose transporter GLUT-4 in muscle membranes. These changes could also be relevant for obesity and type 2 diabetes treatment. Also, the anorectic effect of intermittent hypoxia modulates serotonin and circulating leptin levels, which may contribute to regulate food intake and favor body weight adaptation for optimal sport performance and health. All these actions suggest that intermittent hypoxia can be a very effective tool in sports training as well as in certain clinical protocols.
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Affiliation(s)
| | - Enrique Roche Collado
- Department of Applied Biology-Nutrition. Institute of Bioengineering. Universidad Miguel Hernández
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10
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Mallet RT, Burtscher J, Pialoux V, Pasha Q, Ahmad Y, Millet GP, Burtscher M. Molecular Mechanisms of High-Altitude Acclimatization. Int J Mol Sci 2023; 24:ijms24021698. [PMID: 36675214 PMCID: PMC9866500 DOI: 10.3390/ijms24021698] [Citation(s) in RCA: 57] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/11/2023] [Accepted: 01/13/2023] [Indexed: 01/17/2023] Open
Abstract
High-altitude illnesses (HAIs) result from acute exposure to high altitude/hypoxia. Numerous molecular mechanisms affect appropriate acclimatization to hypobaric and/or normobaric hypoxia and curtail the development of HAIs. The understanding of these mechanisms is essential to optimize hypoxic acclimatization for efficient prophylaxis and treatment of HAIs. This review aims to link outcomes of molecular mechanisms to either adverse effects of acute high-altitude/hypoxia exposure or the developing tolerance with acclimatization. After summarizing systemic physiological responses to acute high-altitude exposure, the associated acclimatization, and the epidemiology and pathophysiology of various HAIs, the article focuses on molecular adjustments and maladjustments during acute exposure and acclimatization to high altitude/hypoxia. Pivotal modifying mechanisms include molecular responses orchestrated by transcription factors, most notably hypoxia inducible factors, and reciprocal effects on mitochondrial functions and REDOX homeostasis. In addition, discussed are genetic factors and the resultant proteomic profiles determining these hypoxia-modifying mechanisms culminating in successful high-altitude acclimatization. Lastly, the article discusses practical considerations related to the molecular aspects of acclimatization and altitude training strategies.
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Affiliation(s)
- Robert T. Mallet
- Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX 76107, USA
| | - Johannes Burtscher
- Department of Biomedical Sciences, University of Lausanne, CH-1005 Lausanne, Switzerland
- Institute of Sport Sciences, University of Lausanne, CH-1005 Lausanne, Switzerland
| | - Vincent Pialoux
- Inter-University Laboratory of Human Movement Biology EA7424, University Claude Bernard Lyon 1, University of Lyon, FR-69008 Lyon, France
| | - Qadar Pasha
- Institute of Hypoxia Research, New Delhi 110067, India
| | - Yasmin Ahmad
- Defense Institute of Physiology & Allied Sciences (DIPAS), Defense Research & Development Organization(DRDO), New Delhi 110054, India
| | - Grégoire P. Millet
- Department of Biomedical Sciences, University of Lausanne, CH-1005 Lausanne, Switzerland
- Institute of Sport Sciences, University of Lausanne, CH-1005 Lausanne, Switzerland
| | - Martin Burtscher
- Department of Sport Science, University of Innsbruck, A-6020 Innsbruck, Austria
- Austrian Society for Alpine and High-Altitude Medicine, A-6020 Innsbruck, Austria
- Correspondence:
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11
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Guerrero-Pinzón JJ, Alcantara JM, García-Buendia G, Mochón-Benguigui S, Ramírez-Maldonado M, Ruiz JR, Jurado-Fasoli L. A nutritional intervention for moderate altitude endurance preparation: A case report. J Int Soc Sports Nutr 2022; 19:650-663. [DOI: 10.1080/15502783.2022.2140596] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
- Juan J. Guerrero-Pinzón
- PROmoting FITness and Health through Physical Activity Research Group (PROFITH), Sport and Health University Research Institute (iMUDS), University of Granada, Department of Physical Education and Sports, Faculty of Sport Sciences, Granada, Spain
| | - Juan M.A. Alcantara
- PROmoting FITness and Health through Physical Activity Research Group (PROFITH), Sport and Health University Research Institute (iMUDS), University of Granada, Department of Physical Education and Sports, Faculty of Sport Sciences, Granada, Spain
| | - Gustavo García-Buendia
- University of Granada, Department Physical Education and Sports, Faculty of Sport Sciences, Granada, Spain
| | - Sol Mochón-Benguigui
- University of Granada, Department of Physiology. Faculty of Medicine, Granada, Spain
| | - Mauricio Ramírez-Maldonado
- PROmoting FITness and Health through Physical Activity Research Group (PROFITH), Sport and Health University Research Institute (iMUDS), University of Granada, Department of Physical Education and Sports, Faculty of Sport Sciences, Granada, Spain
| | - Jonatan R. Ruiz
- PROmoting FITness and Health through Physical Activity Research Group (PROFITH), Sport and Health University Research Institute (iMUDS), University of Granada, Department of Physical Education and Sports, Faculty of Sport Sciences, Granada, Spain
- Instituto de Investigación Biosanitaria, ibs.Granada, Granada, Spain
| | - Lucas Jurado-Fasoli
- PROmoting FITness and Health through Physical Activity Research Group (PROFITH), Sport and Health University Research Institute (iMUDS), University of Granada, Department of Physical Education and Sports, Faculty of Sport Sciences, Granada, Spain
- University of Granada, Department of Physiology. Faculty of Medicine, Granada, Spain
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12
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Kindlovits R, Pereira AMDS, Sousa AC, Viana JL, Teixeira VH. Effects of Acute and Chronic Exercise in Hypoxia on Cardiovascular and Glycemic Parameters in Patients with Type 2 Diabetes: A Systematic Review. High Alt Med Biol 2022; 23:301-312. [PMID: 36036723 DOI: 10.1089/ham.2022.0029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Kindlovits, Raquel, Alberto Mello da Silva Pereira, Ana Catarina Sousa, João Luís Viana,and Vitor Hugo Teixeira. Effects of acute and chronic exercise in hypoxia on cardiovascular and glycemic parameters in patients with type 2 diabetes: a systematic review. High Alt Med Biol. 23:301-312, 2022. Background: Exercise in hypoxia (EH, decreased oxygen availability) has been proposed as a potential therapeutic intervention to promote angiogenesis and improve glucose metabolism to a greater extent than exercise under normoxia (normal ambient air) in patients with type 2 diabetes (T2D). Currently, there are no studies that systematize the existent evidence. This study aims to systematically review the literature and qualitatively evaluate the effects of acute and chronic EH on cardiovascular and glycemic parameters in T2D patients. Methods: A structured search was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines until March 2021, in the MEDLINE/PubMed, Scopus, and Web of Science databases. The inclusion criteria were as follows: (1) randomized and nonrandomized trials, (2) in complication-free patients with T2D, (3) in which EH was compared with exercise in normoxia or with baseline data, and (4) published in English. Results: Six articles (64 subjects) met the inclusion criteria and were reviewed to data extraction. Four articles investigated the acute effect of EH (33 subjects), and two articles investigated the chronic effect of EH (31 subjects), ranging from 6 to 8 weeks. All studies used a cycle ergometer as exercise. Acute EH benefits insulin sensitivity, blood glucose, vascular endothelial growth factor, and metalloproteinase-9, while chronic EH benefits nitric oxide synthase in erythrocytes, but not brachial artery flow-mediated dilation. Conclusion: Acute EH improves glucose homeostasis in T2D patients, which was not seen with chronic EH. Both acute EH and chronic EH improve angiogenesis regulators, but not vascular function. Despite the putative benefits of EH in patients with T2D, the evidence is still scarce and further research is needed before recommendations can be provided.
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Affiliation(s)
- Raquel Kindlovits
- Faculty of Nutrition and Food Sciences, University of Porto (FCNAUP), Porto, Portugal
| | | | - Ana Catarina Sousa
- Research Center in Sports Sciences, Health Sciences and Human Development (CIDESD), University of Maia, Maia, Portugal
| | - João Luís Viana
- Research Center in Sports Sciences, Health Sciences and Human Development (CIDESD), University of Maia, Maia, Portugal
| | - Vitor Hugo Teixeira
- Faculty of Nutrition and Food Sciences, University of Porto (FCNAUP), Porto, Portugal.,Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sports, University of Porto (FADEUP), Portugal.,Laboratory for Integrative and Translational Research in Population Health (ITR), Porto, Portugal
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13
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Hypoxia as a Double-Edged Sword to Combat Obesity and Comorbidities. Cells 2022; 11:cells11233735. [PMID: 36496995 PMCID: PMC9736735 DOI: 10.3390/cells11233735] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 11/14/2022] [Accepted: 11/17/2022] [Indexed: 11/24/2022] Open
Abstract
The global epidemic of obesity is tightly associated with numerous comorbidities, such as type II diabetes, cardiovascular diseases and the metabolic syndrome. Among the key features of obesity, some studies have suggested the abnormal expansion of adipose-tissue-induced local endogenous hypoxic, while other studies indicated endogenous hyperoxia as the opposite trend. Endogenous hypoxic aggravates dysfunction in adipose tissue and stimulates secretion of inflammatory molecules, which contribute to obesity. In contrast, hypoxic exposure combined with training effectively generate exogenous hypoxic to reduce body weight and downregulate metabolic risks. The (patho)physiological effects in adipose tissue are distinct from those of endogenous hypoxic. We critically assess the latest advances on the molecular mediators of endogenous hypoxic that regulate the dysfunction in adipose tissue. Subsequently we propose potential therapeutic targets in adipose tissues and the small molecules that may reverse the detrimental effect of local endogenous hypoxic. More importantly, we discuss alterations of metabolic pathways in adipose tissue and the metabolic benefits brought by hypoxic exercise. In terms of therapeutic intervention, numerous approaches have been developed to treat obesity, nevertheless durability and safety remain the major concern. Thus, a combination of the therapies that suppress endogenous hypoxic with exercise plans that augment exogenous hypoxic may accelerate the development of more effective and durable medications to treat obesity and comorbidities.
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14
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Dugan CW, Maloney SK, Abramoff KJ, Panag SS, Davis EA, Jones TW, Fournier PA. Effects of Simulated High Altitude on Blood Glucose Levels During Exercise in Individuals With Type 1 Diabetes. J Clin Endocrinol Metab 2022; 107:1375-1382. [PMID: 34935935 DOI: 10.1210/clinem/dgab881] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT Current exercise guidelines for individuals with type 1 diabetes (T1D) do not consider the impact that high altitude may have on blood glucose levels (BGL) during exercise. OBJECTIVE To investigate the effect of acute hypoxia (simulated high altitude) on BGL and carbohydrate oxidation rates during moderate intensity exercise in individuals with T1D. METHODS Using a counterbalanced, repeated measures study design, 7 individuals with T1D completed 2 exercise sessions; normoxia and hypoxia (~4200 m simulated altitude). Participants cycled for 60 min on an ergometer at 45% of their sea-level V̇O2peak, and then recovered for 60 min. Before, during, and after exercise, blood samples were taken to measure glucose, lactate, and insulin levels. Respiratory gases were collected to measure carbohydrate oxidation rates. RESULTS Early during exercise (<30 min), there was no fall in BGL in either condition. After 1 h of exercise and during recovery, BGL were significantly lower under the hypoxic condition compared to both pre-exercise levels (P = 0.008) and the normoxic condition (P = 0.027). Exercise in both conditions resulted in a significant rise in carbohydrate oxidation rates, which returned to baseline levels postexercise. Before, during, and after exercise, carbohydrate oxidation rates were higher under the hypoxic compared with the normoxic condition (P < 0.001). CONCLUSIONS The greater decline in BGL during and after exercise performed under acute hypoxia suggests that exercise during acute exposure to high altitude may increase the risk of hypoglycemia in individuals with T1D. Future guidelines may have to consider the impact altitude has on exercise-mediated hypoglycemia.
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Affiliation(s)
- Cory W Dugan
- Department of Sport Science, Exercise and Health, School of Human Sciences, The University of Western Australia, Crawley, Australia
| | - Shane K Maloney
- Department of Sport Science, Exercise and Health, School of Human Sciences, The University of Western Australia, Crawley, Australia
| | - Kristina J Abramoff
- Department of Sport Science, Exercise and Health, School of Human Sciences, The University of Western Australia, Crawley, Australia
| | - Sohan S Panag
- Department of Sport Science, Exercise and Health, School of Human Sciences, The University of Western Australia, Crawley, Australia
| | - Elizabeth A Davis
- Childrens Diabetes Centre, Telethon Kids Institute, Nedlands, Australia
| | - Timothy W Jones
- Childrens Diabetes Centre, Telethon Kids Institute, Nedlands, Australia
| | - Paul A Fournier
- Department of Sport Science, Exercise and Health, School of Human Sciences, The University of Western Australia, Crawley, Australia
- Childrens Diabetes Centre, Telethon Kids Institute, Nedlands, Australia
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15
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Brooks GA, Osmond AD, Leija RG, Curl CC, Arevalo JA, Duong JJ, Horning MA. The blood lactate/pyruvate equilibrium affair. Am J Physiol Endocrinol Metab 2022; 322:E34-E43. [PMID: 34719944 PMCID: PMC8722269 DOI: 10.1152/ajpendo.00270.2021] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
The Lactate Shuttle hypothesis is supported by a variety of techniques including mass spectrometry analytics following infusion of carbon-labeled isotopic tracers. However, there has been controversy over whether lactate tracers measure lactate (L) or pyruvate (P) turnover. Here, we review the analytical errors, use of inappropriate tissue and animal models, failure to consider L and P pool sizes in modeling results, inappropriate tracer and blood sampling sites, and failure to anticipate roles of heart and lung parenchyma on L⇔P interactions. With support from magnetic resonance spectroscopy (MRS) and immunocytochemistry, we conclude that carbon-labeled lactate tracers can be used to quantitate lactate fluxes.
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Affiliation(s)
- George A Brooks
- Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, California
| | - Adam D Osmond
- Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, California
| | - Robert G Leija
- Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, California
| | - Casey C Curl
- Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, California
| | - Jose A Arevalo
- Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, California
| | - Justin J Duong
- Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, California
| | - Michael A Horning
- Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, California
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16
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Early Blood Glucose Level Post-Admission Correlates with the Outcomes and Oxidative Stress in Neonatal Hypoxic-Ischemic Encephalopathy. Antioxidants (Basel) 2021; 11:antiox11010039. [PMID: 35052543 PMCID: PMC8773159 DOI: 10.3390/antiox11010039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 12/19/2021] [Accepted: 12/23/2021] [Indexed: 12/25/2022] Open
Abstract
The antioxidant defense system is involved in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). To analyze the relationship between first serum blood glucose levels and outcomes in neonatal HIE, seventy-four patients were divided, based on the first glucose level, into group 1 (>0 mg/dL and <60 mg/dL, n =11), group 2 (≥60 mg/dL and <150 mg/dL, n = 49), and group 3 (≥150 mg/dL, n = 14). Abnormal glucose levels had poor outcomes among three groups in terms of the clinical stage (p = 0.001), brain parenchymal lesion (p = 0.004), and neurodevelopmental outcomes (p = 0.029). Hearing impairment was more common in group 3 than in group 1 (p = 0.062) and group 2 (p = 0.010). The MRI findings of group 3 exhibited more thalamus and basal ganglion lesions than those of group 1 (p = 0.012). The glucose level was significantly correlated with clinical staging (p< 0.001), parenchymal brain lesions (p = 0.044), hearing impairment (p = 0.003), and neurodevelopmental outcomes (p = 0.005) by Pearson’s test. The first blood glucose level in neonatal HIE is an important biomarker for clinical staging, MRI findings, as well as hearing and neurodevelopment outcomes. Hyperglycemic patients had a higher odds ratio for thalamus, basal ganglia, and brain stem lesions than hypoglycemic patients with white matter and focal ischemic injury. Hyperglycemia can be due to prolonged or intermittent hypoxia and can be associated with poor outcomes.
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17
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van Meijel RLJ, Vogel MAA, Jocken JWE, Vliex LMM, Smeets JSJ, Hoebers N, Hoeks J, Essers Y, Schoffelen PFM, Sell H, Kersten S, M A Rouschop K, Blaak EE, Goossens GH. Mild intermittent hypoxia exposure induces metabolic and molecular adaptations in men with obesity. Mol Metab 2021; 53:101287. [PMID: 34224918 PMCID: PMC8355948 DOI: 10.1016/j.molmet.2021.101287] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 06/15/2021] [Accepted: 06/30/2021] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE Recent studies suggest that hypoxia exposure may improve glucose homeostasis, but well-controlled human studies are lacking. We hypothesized that mild intermittent hypoxia (MIH) exposure decreases tissue oxygen partial pressure (pO2) and induces metabolic improvements in people who are overweight/obese. METHODS In a randomized, controlled, single-blind crossover study, 12 men who were overweight/obese were exposed to MIH (15 % O2, 3 × 2 h/day) or normoxia (21 % O2) for 7 consecutive days. Adipose tissue (AT) and skeletal muscle (SM) pO2, fasting/postprandial substrate metabolism, tissue-specific insulin sensitivity, SM oxidative capacity, and AT and SM gene/protein expression were determined. Furthermore, primary human myotubes and adipocytes were exposed to oxygen levels mimicking the hypoxic and normoxic AT and SM microenvironments. RESULTS MIH decreased systemic oxygen saturation (92.0 ± 0.5 % vs 97.1 ± 0.3, p < 0.001, respectively), AT pO2 (21.0 ± 2.3 vs 36.5 ± 1.5 mmHg, p < 0.001, respectively), and SM pO2 (9.5 ± 2.2 vs 15.4 ± 2.4 mmHg, p = 0.002, respectively) compared to normoxia. In addition, MIH increased glycolytic metabolism compared to normoxia, reflected by enhanced fasting and postprandial carbohydrate oxidation (pAUC = 0.002) and elevated plasma lactate concentrations (pAUC = 0.005). Mechanistically, hypoxia exposure increased insulin-independent glucose uptake compared to standard laboratory conditions (~50 %, p < 0.001) and physiological normoxia (~25 %, p = 0.019) through AMP-activated protein kinase in primary human myotubes but not in primary human adipocytes. MIH upregulated inflammatory/metabolic pathways and downregulated extracellular matrix-related pathways in AT but did not alter systemic inflammatory markers and SM oxidative capacity. MIH exposure did not induce significant alterations in AT (p = 0.120), hepatic (p = 0.132) and SM (p = 0.722) insulin sensitivity. CONCLUSIONS Our findings demonstrate for the first time that 7-day MIH reduces AT and SM pO2, evokes a shift toward glycolytic metabolism, and induces adaptations in AT and SM but does not induce alterations in tissue-specific insulin sensitivity in men who are overweight/obese. Future studies are needed to investigate further whether oxygen signaling is a promising target to mitigate metabolic complications in obesity. CLINICAL TRIAL REGISTRATION This study is registered at the Netherlands Trial Register (NL7120/NTR7325).
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Affiliation(s)
- Rens L J van Meijel
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center(+), Maastricht, the Netherlands
| | - Max A A Vogel
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center(+), Maastricht, the Netherlands
| | - Johan W E Jocken
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center(+), Maastricht, the Netherlands
| | - Lars M M Vliex
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center(+), Maastricht, the Netherlands
| | - Joey S J Smeets
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center(+), Maastricht, the Netherlands
| | - Nicole Hoebers
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center(+), Maastricht, the Netherlands
| | - Joris Hoeks
- Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center(+), Maastricht, the Netherlands
| | - Yvonne Essers
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center(+), Maastricht, the Netherlands
| | - Paul F M Schoffelen
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center(+), Maastricht, the Netherlands; Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center(+), Maastricht, the Netherlands
| | - Henrike Sell
- Paul-Langerhans-Group for Integrative Physiology, German Diabetes Center, Dusseldorf, Germany
| | - Sander Kersten
- Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands
| | - Kasper M A Rouschop
- Maastricht Radiation Oncology (MaastRO) Laboratory, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center(+), Maastricht, the Netherlands
| | - Ellen E Blaak
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center(+), Maastricht, the Netherlands
| | - Gijs H Goossens
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center(+), Maastricht, the Netherlands.
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18
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Increased Reliance on Carbohydrates for Aerobic Exercise in Highland Andean Leaf-Eared Mice, but Not in Highland Lima Leaf-Eared Mice. Metabolites 2021; 11:metabo11110750. [PMID: 34822408 PMCID: PMC8618444 DOI: 10.3390/metabo11110750] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Revised: 10/27/2021] [Accepted: 10/27/2021] [Indexed: 11/17/2022] Open
Abstract
Exercise is an important performance trait in mammals and variation in aerobic capacity and/or substrate allocation during submaximal exercise may be important for survival at high altitude. Comparisons between lowland and highland populations is a fruitful approach to understanding the mechanisms for altitude differences in exercise performance. However, it has only been applied in very few highland species. The leaf-eared mice (LEM, genus Phyllotis) of South America are a promising taxon to uncover the pervasiveness of hypoxia tolerance mechanisms. Here we use lowland and highland populations of Andean and Lima LEM (P. andium and P. limatus), acclimated to common laboratory conditions, to determine exercise-induced maximal oxygen consumption (V˙O2max), and submaximal exercise metabolism. Lowland and highland populations of both species showed no difference in V˙O2max running in either normoxia or hypoxia. When run at 75% of V˙O2max, highland Andean LEM had a greater reliance on carbohydrate oxidation to power exercise. In contrast, highland Lima LEM showed no difference in exercise fuel use compared to their lowland counterparts. The higher carbohydrate oxidation seen in highland Andean LEM was not explained by maximal activities of glycolytic enzymes in the gastrocnemius muscle, which were equivalent to lowlanders. This result is consistent with data on highland deer mouse populations and suggests changes in metabolic regulation may explain altitude differences in exercise performance.
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19
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Paris HL, Sinai EC, Shei RJ, Keller AM, Mickleborough TD. The influence of carbohydrate ingestion on peripheral and central fatigue during exercise in hypoxia: A narrative review. Eur J Sport Sci 2021; 21:1423-1435. [PMID: 33106121 PMCID: PMC8140067 DOI: 10.1080/17461391.2020.1842512] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Hypoxia impairs aerobic performance by accelerating fatiguing processes. These processes may originate from sites either distal (peripheral) or proximal (central) to the neuromuscular junction, though these are not mutually exclusive. Peripheral mechanisms include decrements in muscle glycogen or fluctuations in intramuscular metabolites, whereas central responses commonly refer to reductions in central motor drive elicited by alterations in blood glucose and neurotransmitter concentrations as well as arterial hypoxemia. Hypoxia may accelerate both peripheral and central pathways of fatigue, with the level of hypoxia strongly dictating the degree and primary locus of impairment. As more people journey to hypoxic settings for work and recreation, developing strategies to improve work capacity in these environments becomes increasingly relevant. Given that sea level performance improves with nutritional interventions such as carbohydrate (CHO) ingestion, a similar strategy may prove effective in delaying fatigue in hypoxia, particularly considering how the metabolic pathways enhanced with CHO supplementation overlap the fatiguing pathways upregulated in hypoxia. Many questions regarding the relationship between CHO, hypoxia, and fatigue remain unanswered, including specifics on when to ingest, what to ingest, and how varying altitudes influence supplementation effectiveness. Therefore, the purpose of this narrative review is to examine the peripheral and central mechanisms contributing to fatigue during aerobic exercise at varying degrees of hypoxia and to assess the role of CHO ingestion in attenuating fatigue onset.
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Affiliation(s)
- Hunter L Paris
- Department of Sports Medicine, Pepperdine University, Malibu, CA, USA
| | - Erin C Sinai
- Department of Sports Medicine, Pepperdine University, Malibu, CA, USA
| | - Ren-Jay Shei
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, and Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA
| | | | - Timothy D Mickleborough
- Department of Kinesiology, School of Public Health-Bloomington, Indiana University, Bloomington, IN, USA
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20
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Malgoyre A, Prola A, Meunier A, Chapot R, Serrurier B, Koulmann N, Bigard X, Sanchez H. Endurance Is Improved in Female Rats After Living High-Training High Despite Alterations in Skeletal Muscle. Front Sports Act Living 2021; 3:663857. [PMID: 34124658 PMCID: PMC8193088 DOI: 10.3389/fspor.2021.663857] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 04/12/2021] [Indexed: 11/29/2022] Open
Abstract
Altitude camps are used during the preparation of endurance athletes to improve performance based on the stimulation of erythropoiesis by living at high altitude. In addition to such whole-body adaptations, studies have suggested that high-altitude training increases mitochondrial mass, but this has been challenged by later studies. Here, we hypothesized that living and training at high altitude (LHTH) improves mitochondrial efficiency and/or substrate utilization. Female rats were exposed and trained in hypoxia (simulated 3,200 m) for 5 weeks (LHTH) and compared to sedentary rats living in hypoxia (LH) or normoxia (LL) or those that trained in normoxia (LLTL). Maximal aerobic velocity (MAV) improved with training, independently of hypoxia, whereas the time to exhaustion, performed at 65% of MAV, increased both with training (P = 0.009) and hypoxia (P = 0.015), with an additive effect of the two conditions. The distance run was 7.98 ± 0.57 km in LHTH vs. 6.94 ± 0.51 in LLTL (+15%, ns). The hematocrit increased >20% with hypoxia (P < 0.001). The increases in mitochondrial mass and maximal oxidative capacity with endurance training were blunted by combination with hypoxia (−30% for citrate synthase, P < 0.01, and −23% for Vmax glut−succ, P < 0.001 between LHTH and LLTL). A similar reduction between the LHTH and LLTL groups was found for maximal respiration with pyruvate (−29%, P < 0.001), for acceptor-control ratio (−36%, hypoxia effect, P < 0.001), and for creatine kinase efficiency (−48%, P < 0.01). 3-hydroxyl acyl coenzyme A dehydrogenase was not altered by hypoxia, whereas maximal respiration with Palmitoyl-CoA specifically decreased. Overall, our results show that mitochondrial adaptations are not involved in the improvement of submaximal aerobic performance after LHTH, suggesting that the benefits of altitude camps in females relies essentially on other factors, such as the transitory elevation of hematocrit, and should be planned a few weeks before competition and not several months.
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Affiliation(s)
- Alexandra Malgoyre
- Département des Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France.,Laboratoire de Biologie de l'Exercice pour la Performance et la Santé, Université Evry, Université Paris Saclay, Evry, France
| | - Alexandre Prola
- Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Adelie Meunier
- Département des Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France
| | - Rachel Chapot
- Département des Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France
| | - Bernard Serrurier
- Département des Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France
| | - Nathalie Koulmann
- Département des Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France.,Laboratoire de Biologie de l'Exercice pour la Performance et la Santé, Université Evry, Université Paris Saclay, Evry, France.,Ecole du Val de Grâce, Paris, France
| | - Xavier Bigard
- Département des Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France.,Ecole du Val de Grâce, Paris, France
| | - Hervé Sanchez
- Département des Environnements Opérationnels, Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France
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21
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Kim SW, Jung WS, Chung S, Park HY. Exercise intervention under hypoxic condition as a new therapeutic paradigm for type 2 diabetes mellitus: A narrative review. World J Diabetes 2021; 12:331-343. [PMID: 33889283 PMCID: PMC8040082 DOI: 10.4239/wjd.v12.i4.331] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Revised: 01/25/2021] [Accepted: 03/08/2021] [Indexed: 02/06/2023] Open
Abstract
This review aims to summarize the health benefits of exposure to hypoxic conditions during exercise in patients with type 2 diabetes mellitus (T2DM). Exposure to hypoxic conditions during exercise training positively changes the physiological response in healthy subjects. Exposure to hypoxic conditions during exercise could markedly increase skeletal muscle glucose uptake compared to that in normoxic conditions. Furthermore, post-exercise insulin sensitivity of T2DM patients increases more when exercising under hypoxic than under normoxic conditions. Regular exercise under short-term hypoxic conditions can improve blood glucose control at lower workloads than in normoxic conditions. Additionally, exercise training under short-term hypoxic conditions can maximize weight loss in overweight and obese patients. Previous studies on healthy subjects have reported that regular exercise under hypoxic conditions had a more positive effect on vascular health than exercising under normoxic conditions. However, currently, evidence indicating that exposure to hypoxic conditions could positively affect T2DM patients in the long-term is lacking. Therefore, further evaluations of the beneficial effects of exercise under hypoxic conditions on the human body, considering different cycle lengths, duration of exposures, sessions per day, and the number of days, are necessary. In this review, we conclude that there is evidence that exercise under hypoxic conditions can yield health benefits, which is potentially valuable in terms of clinical care as a new intervention for T2DM patients.
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Affiliation(s)
- Sung-Woo Kim
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul 05029, South Korea
| | - Won-Sang Jung
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul 05029, South Korea
| | - Sochung Chung
- Department of Pediatrics, Konkuk University Medical Center, Research Institute of Medical Science, Konkuk University, School of Medicine, Seoul 05029, South Korea
| | - Hun-Young Park
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul 05029, South Korea
- Department of Sports Science and Medicine, Konkuk University, Seoul 05029, South Korea
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22
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Koivisto-Mørk AE, Paur I, Paulsen G, Garthe I, Raastad T, Bastani NE, Blomhoff R, Bøhn SK. Dietary Adjustments to Altitude Training in Elite Endurance Athletes; Impact of a Randomized Clinical Trial With Antioxidant-Rich Foods. Front Sports Act Living 2020; 2:106. [PMID: 33345095 PMCID: PMC7739752 DOI: 10.3389/fspor.2020.00106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 07/14/2020] [Indexed: 11/13/2022] Open
Abstract
Background: Altitude training stresses several physiological and metabolic processes and alters the dietary needs of the athletes. International Olympic Committee (IOC)'s Nutrition Expert Group suggests that athletes should increase intake of energy, carbohydrate, iron, fluid, and antioxidant-rich foods while training at altitude. Objective: We investigated whether athletes adjust their dietary intake according to the IOC's altitude-specific dietary recommendations, and whether an in-between meal intervention with antioxidant-rich foods altered the athletes' dietary composition and nutrition-related blood parameters (mineral, vitamin, carotenoid, and hormone concentrations). Design: The dietary adjustments to altitude training (3 weeks at 2,320 m) were determined for 31 elite endurance athletes (23 ± 5 years, 23 males, 8 females) by six interviewer-administered 24-h dietary recalls on non-consecutive days; three before and during the altitude camp. The additional effect of in -between meal intervention with eucaloric antioxidant-rich or control snacks (1,000 kcal/day) was tested in a randomized controlled trial with parallel design. Results: At altitude the athletes increased their energy intake by 35% (1,430 ± 630 kcal/day, p < 0.001), the provided snacks accounting for 70% of this increase. Carbohydrate intake increased from 6.5 ± 1.8 g/kg body weight (BW) (50 E%) to 9.3 ± 2.1 g/kg BW (53 E%) (p < 0.001), with no difference between the antioxidant and control group. Dietary iron, fluid, and antioxidant-rich food intake increased by 37, 38, and 104%, respectively, in the whole cohort. The intervention group had larger increases in polyunsaturated fatty acids (PUFA), ω3 PUFA (n-3 fatty acids), ω6 PUFA (n-6 fatty acids), fiber, vitamin C, folic acid, and copper intake, while protein intake increased more among the controls, reflecting the nutritional content of the snacks. Changes in the measured blood minerals, vitamins, and hormones were not differentially affected by the intervention except for the carotenoid; zeaxanthin, which increased more in the intervention group (p < 0.001). Conclusions: Experienced elite endurance athletes increased their daily energy, carbohydrate, iron, fluid, and antioxidant-rich food intake during a 3-week training camp at moderate altitude meeting most of the altitude-specific dietary recommendations. The intervention with antioxidant-rich snacks improved the composition of the athletes' diets but had minimal impact on the measured nutrition-related blood parameters. Clinical Trial Registry Number: NCT03088891 (www.clinicaltrials.gov), Norwegian registry number: 626539 (https://rekportalen.no/).
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Affiliation(s)
- Anu E Koivisto-Mørk
- Norwegian Olympic Sports Centre, Norwegian Olympic and Paralympic Committee and Confederation of Sports, Oslo, Norway
| | - Ingvild Paur
- Norwegian National Advisory Unit on Disease-Related Undernutrition, Oslo University Hospital, Oslo, Norway
| | - Gøran Paulsen
- Norwegian Olympic Sports Centre, Norwegian Olympic and Paralympic Committee and Confederation of Sports, Oslo, Norway.,Department of Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway
| | - Ina Garthe
- Norwegian Olympic Sports Centre, Norwegian Olympic and Paralympic Committee and Confederation of Sports, Oslo, Norway
| | - Truls Raastad
- Department of Physical Performance, Norwegian School of Sport Sciences, Oslo, Norway
| | - Nasser E Bastani
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
| | - Rune Blomhoff
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.,Division of Cancer Medicine, Oslo University Hospital, Oslo, Norway
| | - Siv K Bøhn
- Faculty of Chemistry, Biotechnology and Food Sciences, Norwegian University of Life Sciences, Ås, Norway
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Lamo D, Gahlawat G, Kumar S, Bharti VK, Ranjan P, Kumar D, Chaurasia OP. Morphometric, haematological and physio-biochemical characterization of Bactrian (Camelus bactrianus) camel at high altitude. BMC Vet Res 2020; 16:291. [PMID: 32795315 PMCID: PMC7427938 DOI: 10.1186/s12917-020-02481-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 07/20/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Biochemical and haematological parameters have not been determined in Bactrian camels kept at high altitude. Therefore, this study was undertaken to characterise different physiological, haematological, biochemical, and morphometric parameters of Bactrian camels of high altitude. For this, total fourteen high altitude healthy Bactrian camels were selected from Leh-Ladakh, India, a high altitude area, and thereafter divided into three age groups (N = 3 young; N = 6 adult; N = 5 old camels) to characterise for above parameters. All the results were compared with Lowlander Bactrian camels. RESULTS Morphometric measurement showed significant difference in body height, body length, front-hump height and girth, back-hump height and girth, abdomen girth, neck length, and circumference of the shank in the young age group camels as compared to other age groups of Bactrian camels (p < 0.05). Furthermore, all the physiological and haematological parameters were similar in all the age groups of camels (p < 0.05). However, the leukocyte, erythrocyte, Hb, platelets, monocyte, and ESR level were towards the higher side of the normal reference range of Lowlander Bactrian camels. Whereas, the biochemical analysis revealed a significant increase in triglycerides and decrease in protein levels in the younger age group as compared to other age groups (p < 0.05). Although, albumin, aspartate aminotransferase, iron, magnesium, urea, and creatinine levels were insignificant among the different groups, but observed towards the higher side of the low altitude reference range. Interestingly, the glucose levels in all the groups were observed towards the lower side of the range, which showed metabolic adaptation to high altitude. CONCLUSION These findings suggested there is morphometric and biochemical variation in Bactrian camel of high altitude. The results further helped in establishing novel reference ranges for these parameters in Highlander Bactrian camel. Hence, this study will be the basis of future research on a Bactrian camel from high-altitude cold desert and helpful for better camel husbandry and health management in high altitude.
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Affiliation(s)
- Dolker Lamo
- DRDO-Defence Institute of High Altitude Research (DIHAR), Leh, Ladakh, UT-194101, India
| | - Geeta Gahlawat
- DRDO-Defence Institute of High Altitude Research (DIHAR), Leh, Ladakh, UT-194101, India
| | - Sunil Kumar
- DRDO-Defence Institute of High Altitude Research (DIHAR), Leh, Ladakh, UT-194101, India
| | - Vijay K Bharti
- DRDO-Defence Institute of High Altitude Research (DIHAR), Leh, Ladakh, UT-194101, India.
| | - Puneet Ranjan
- DRDO-Defence Institute of High Altitude Research (DIHAR), Leh, Ladakh, UT-194101, India
| | - Deepak Kumar
- DRDO-Defence Institute of High Altitude Research (DIHAR), Leh, Ladakh, UT-194101, India
| | - Om Prakash Chaurasia
- DRDO-Defence Institute of High Altitude Research (DIHAR), Leh, Ladakh, UT-194101, India
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Hara Y, Watanabe N. Changes in expression of genes related to glucose metabolism in liver and skeletal muscle of rats exposed to acute hypoxia. Heliyon 2020; 6:e04334. [PMID: 32642586 PMCID: PMC7334421 DOI: 10.1016/j.heliyon.2020.e04334] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 02/01/2019] [Accepted: 06/24/2020] [Indexed: 02/08/2023] Open
Abstract
The aim of this study was to determine changes in gene expression associated with glucose metabolism in the liver and soleus muscles of rats exposed to hypoxia to improve work capacity under high altitude conditions. Rats were divided into normobaric normoxia (control) and normobaric hypoxia (hypoxia) groups (n = 7 each), and the hypoxia group was exposed to 10.5% oxygen for 90 min. Glucose metabolism-related gene expression was examined by real-time polymerase chain reaction. In the liver, the expression levels of the glucose utilization-related genes solute carrier family 2 member 1, glucokinase, and liver-type phosphofructokinase and the gluconeogenesis-related gene phosphoenolpyruvate carboxykinase 1 (Pck1) were significantly increased upon hypoxic exposure. In contrast, gene expression in the soleus was unchanged, with the exception of Pck1. The results suggest that under hypoxia, both glucose utilization and gluconeogenesis are accelerated in the liver, and liver glycogen is degraded to maintain blood glucose level.
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Affiliation(s)
- Yurie Hara
- Department of Nutritional Science, Tokyo Kasei University, 1-18-1 Kaga, Itabashi, Tokyo, 173-8602, Japan
| | - Nakamichi Watanabe
- Department of Health Science, Showa Women's University, 1-7-57 Taishido, Setagaya, Tokyo, 154-8533, Japan
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25
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Hypoxic Exposure Increases Energy Expenditure by Increasing Carbohydrate Oxidation in Mice. BIOMED RESEARCH INTERNATIONAL 2020. [DOI: 10.1155/2020/6159407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Aims. Hypoxic exposure improves glucose metabolism. We investigated to validate the hypothesis that carbohydrate (CHO) oxidation could increase in mice exposed to severe hypoxic conditions.Methods. Seven-week-old male ICR mice (n=16) were randomly divided into two groups: the control group (CON) was kept in normoxic condition (fraction of inspiredO2=21%) and the hypoxia group (HYP) was exposed to hypoxic condition (fraction of inspiredO2=12%, ≈altitude of 4,300 m). The CON group was pair-fed with the HYP group. After 3 weeks of hypoxic exposure, we measured respiratory metabolism (energy expenditure and substrate utilization) at normoxic conditions for 24 hours using an open-circuit calorimetry system. In addition, we investigated changes in carbohydrate mechanism-related protein expression, including hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), and regulator of the genes involved in energy metabolism (peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC1α) in soleus muscle.Results. Energy expenditure (EE) and CHO oxidation over 24 hours were higher in the HYP group by approximately 15% and 34% (p<0.001), respectively. Fat oxidation was approximately 29% lower in the HYP group than the CON group (p<0.01). Body weight gains were significantly lower in the HYP group than in the CON group (CON vs. HYP;1.9±0.9vs.−0.3±0.9;p<0.001). Hypoxic exposure for 3 weeks significantly reduced body fat by approximately 42% (p<0.001). PDH and PGC1αprotein levels were significantly higher in the HYP group (p<0.05). Additionally, HK2 was approximately 21% higher in the HYP group.Conclusions. Hypoxic exposure might significantly enhance CHO oxidation by increasing the expression of PDH and HK2. This investigation can be useful for patients with impaired glucose metabolism, such as those with type 2 diabetes.
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O'Hara JP, Duckworth L, Black A, Woods DR, Mellor A, Boos C, Gallagher L, Tsakirides C, Arjomandkhah NC, Morrison DJ, Preston T, King RFGJ. Fuel Use during Exercise at Altitude in Women with Glucose-Fructose Ingestion. Med Sci Sports Exerc 2020; 51:2586-2594. [PMID: 31206498 DOI: 10.1249/mss.0000000000002072] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
PURPOSE This study compared the coingestion of glucose and fructose on exogenous and endogenous substrate oxidation during prolonged exercise at terrestrial high altitude (HA) versus sea level, in women. METHOD Five women completed two bouts of cycling at the same relative workload (55% Wmax) for 120 min on acute exposure to HA (3375 m) and at sea level (~113 m). In each trial, participants ingested 1.2 g·min of glucose (enriched with C glucose) and 0.6 g·min of fructose (enriched with C fructose) before and every 15 min during exercise. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate fat oxidation, total and exogenous carbohydrate oxidation, plasma glucose oxidation, and endogenous glucose oxidation derived from liver and muscle glycogen. RESULTS The rates and absolute contribution of exogenous carbohydrate oxidation was significantly lower at HA compared with sea level (effect size [ES] > 0.99, P < 0.024), with the relative exogenous carbohydrate contribution approaching significance (32.6% ± 6.1% vs 36.0% ± 6.1%, ES = 0.56, P = 0.059) during the second hour of exercise. In comparison, no significant differences were observed between HA and sea level for the relative and absolute contributions of liver glucose (3.2% ± 1.2% vs 3.1% ± 0.8%, ES = 0.09, P = 0.635 and 5.1 ± 1.8 vs 5.4 ± 1.7 g, ES = 0.19, P = 0.217), and muscle glycogen (14.4% ± 12.2% vs 15.8% ± 9.3%, ES = 0.11, P = 0.934 and 23.1 ± 19.0 vs 28.7 ± 17.8 g, ES = 0.30, P = 0.367). Furthermore, there was no significant difference in total fat oxidation between HA and sea level (66.3 ± 21.4 vs 59.6 ± 7.7 g, ES = 0.32, P = 0.557). CONCLUSIONS In women, acute exposure to HA reduces the reliance on exogenous carbohydrate oxidation during cycling at the same relative exercise intensity.
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Affiliation(s)
- John P O'Hara
- Research Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, UNITED KINGDOM
| | - Lauren Duckworth
- Research Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, UNITED KINGDOM
| | - Alistair Black
- Research Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, UNITED KINGDOM
| | - David R Woods
- Research Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, UNITED KINGDOM.,Royal Centre for Defence Medicine, Birmingham, UNITED KINGDOM.,Northumbria NHS Trust and Newcastle Trust, UNITED KINGDOM
| | - Adrian Mellor
- Research Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, UNITED KINGDOM.,Royal Centre for Defence Medicine, Birmingham, UNITED KINGDOM.,James Cook University Hospital, Middlesborough, UNITED KINGDOM
| | - Christopher Boos
- Research Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, UNITED KINGDOM.,Department of Cardiology, Poole Hospital, Poole, Dorset, UNITED KINGDOM
| | - Liam Gallagher
- Research Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, UNITED KINGDOM
| | - Costas Tsakirides
- Research Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, UNITED KINGDOM
| | - Nicola C Arjomandkhah
- School of Social and Health Sciences, Leeds Trinity University, Leeds, UNITED KINGDOM
| | - Douglas J Morrison
- Scottish Universities Environmental Research Centre, University of Glasgow, East Kilbridge, UNITED KINGDOM
| | - Thomas Preston
- Scottish Universities Environmental Research Centre, University of Glasgow, East Kilbridge, UNITED KINGDOM
| | - Roderick F G J King
- Research Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, UNITED KINGDOM
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Nutrition and Altitude: Strategies to Enhance Adaptation, Improve Performance and Maintain Health: A Narrative Review. Sports Med 2020; 49:169-184. [PMID: 31691928 PMCID: PMC6901429 DOI: 10.1007/s40279-019-01159-w] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Training at low to moderate altitudes (~ 1600-2400 m) is a common approach used by endurance athletes to provide a distinctive environmental stressor to augment training stimulus in the anticipation of increasing subsequent altitude- and sea-level-based performance. Despite some scientific progress being made on the impact of various nutrition-related changes in physiology and associated interventions at mountaineering altitudes (> 3000 m), the impact of nutrition and/or supplements on further optimization of these hypoxic adaptations at low-moderate altitudes is only an emerging topic. Within this narrative review we have highlighted six major themes involving nutrition: altered energy availability, iron, carbohydrate, hydration, antioxidant requirements and various performance supplements. Of these issues, emerging data suggest that particular attention be given to the potential risk for poor energy availability and increased iron requirements at the altitudes typical of elite athlete training (~ 1600-2400 m) to interfere with optimal adaptations. Furthermore, the safest way to address the possible increase in oxidative stress associated with altitude exposure is via the consumption of antioxidant-rich foods rather than high-dose antioxidant supplements. Meanwhile, many other important questions regarding nutrition and altitude training remain to be answered. At the elite level of sport where the differences between winning and losing are incredibly small, the strategic use of nutritional interventions to enhance the adaptations to altitude training provides an important consideration in the search for optimal performance.
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28
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Pasiakos SM. Nutritional Requirements for Sustaining Health and Performance During Exposure to Extreme Environments. Annu Rev Nutr 2020; 40:221-245. [PMID: 32530730 DOI: 10.1146/annurev-nutr-011720-122637] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Dietary guidelines are formulated to meet minimum nutrient requirements, which prevent deficiencies and maintain health, growth, development, and function. These guidelines can be inadequate and contribute to disrupted homeostasis, lean body mass loss, and deteriorated performance in individuals who are working long, arduous hours with limited access to food in environmentally challenging locations. Environmental extremes can elicit physiological adjustments that alone alter nutrition requirements by upregulating energy expenditure, altering substrate metabolism, and accelerating body water and muscle protein loss. The mechanisms by which the environment, including high-altitude, heat, and cold exposure, alters nutrition requirements have been studied extensively. This contemporary review discusses physiological adjustments to environmental extremes, particularly when those adjustments alter dietary requirements.
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Affiliation(s)
- Stefan M Pasiakos
- Military Nutrition Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts 01760, USA;
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29
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Evans AM, Hardie DG. AMPK and the Need to Breathe and Feed: What's the Matter with Oxygen? Int J Mol Sci 2020; 21:ijms21103518. [PMID: 32429235 PMCID: PMC7279029 DOI: 10.3390/ijms21103518] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 05/11/2020] [Accepted: 05/12/2020] [Indexed: 12/12/2022] Open
Abstract
We live and to do so we must breathe and eat, so are we a combination of what we eat and breathe? Here, we will consider this question, and the role in this respect of the AMP-activated protein kinase (AMPK). Emerging evidence suggests that AMPK facilitates central and peripheral reflexes that coordinate breathing and oxygen supply, and contributes to the central regulation of feeding and food choice. We propose, therefore, that oxygen supply to the body is aligned with not only the quantity we eat, but also nutrient-based diet selection, and that the cell-specific expression pattern of AMPK subunit isoforms is critical to appropriate system alignment in this respect. Currently available information on how oxygen supply may be aligned with feeding and food choice, or vice versa, through our motivation to breathe and select particular nutrients is sparse, fragmented and lacks any integrated understanding. By addressing this, we aim to provide the foundations for a clinical perspective that reveals untapped potential, by highlighting how aberrant cell-specific changes in the expression of AMPK subunit isoforms could give rise, in part, to known associations between metabolic disease, such as obesity and type 2 diabetes, sleep-disordered breathing, pulmonary hypertension and acute respiratory distress syndrome.
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Affiliation(s)
- A. Mark Evans
- Centre for Discovery Brain Sciences and Cardiovascular Science, Edinburgh Medical School, Hugh Robson Building, University of Edinburgh, Edinburgh EH8 9XD, UK
- Correspondence:
| | - D. Grahame Hardie
- Division of Cell Signalling and Immunology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK;
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Chemerin: A Potential Regulator of Inflammation and Metabolism for Chronic Obstructive Pulmonary Disease and Pulmonary Rehabilitation. BIOMED RESEARCH INTERNATIONAL 2020; 2020:4574509. [PMID: 32337250 PMCID: PMC7166297 DOI: 10.1155/2020/4574509] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 03/05/2020] [Accepted: 03/23/2020] [Indexed: 01/09/2023]
Abstract
Chronic obstructive pulmonary disease (COPD) features chronic inflammatory reactions of both intra- and extrapulmonary nature. Moreover, COPD is associated with abnormal glucose and lipid metabolism in patients, which influences the prognosis and chronicity of this disease. Abnormal glucose and lipid metabolism are also closely related to inflammation processes. Further insights into the interactions of inflammation and glucose and lipid metabolism might therefore inspire novel therapeutic interventions to promote lung rehabilitation. Chemerin, as a recently discovered adipokine, has been shown to play a role in inflammatory response and glucose and lipid metabolism in many diseases (including COPD). Chemerin recruits inflammatory cells to sites of inflammation during the early stages of COPD, leading to endothelial barrier dysfunction, early vascular remodeling, and angiogenesis. Moreover, it supports the recruitment of antigen-presenting cells that guide immune cells as part of the body's inflammatory responses. Chemerin also regulates metabolism via activation of its cognate receptors. Glucose homeostasis is affected via effects on insulin secretion and sensitivity, and lipid metabolism is changed by increased transformation of preadipocytes to mature adipocytes through chemerin-binding receptors. Controlling chemerin signaling may be a promising approach to improve various aspects of COPD-related dysfunction. Importantly, several studies indicate that chemerin expression in vivo is influenced by exercise. Although available evidence is still limited, therapeutic alterations of chemerin activity may be a promising target of therapeutic approaches aimed at the rehabilitation of COPD patients based on exercises. In conclusion, chemerin plays an essential role in COPD, especially in the inflammatory responses and metabolism, and has a potential to become a target for, and a biomarker of, curative mechanisms underlying exercise-mediated lung rehabilitation.
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Margolis LM, Wilson MA, Whitney CC, Carrigan CT, Murphy NE, Radcliffe PN, Gwin JA, Church DD, Wolfe RR, Ferrando AA, Young AJ, Pasiakos SM. Acute hypoxia reduces exogenous glucose oxidation, glucose turnover, and metabolic clearance rate during steady-state aerobic exercise. Metabolism 2020; 103:154030. [PMID: 31778707 DOI: 10.1016/j.metabol.2019.154030] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 10/30/2019] [Accepted: 11/25/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Exogenous carbohydrate oxidation is lower during steady-state aerobic exercise in native lowlanders sojourning at high altitude (HA) compared to sea level (SL). However, the underlying mechanism contributing to reduction in exogenous carbohydrate oxidation during steady-state aerobic exercise performed at HA has not been explored. OBJECTIVE To determine if alterations in glucose rate of appearance (Ra), disappearance (Rd) and metabolic clearance rate (MCR) at HA provide a mechanism for explaining the observation of lower exogenous carbohydrate oxidation compared to during metabolically-matched, steady-state exercise at SL. METHODS Using a randomized, crossover design, native lowlanders (n = 8 males, mean ± SD, age: 23 ± 2 yr, body mass: 87 ± 10 kg, and VO2peak: SL 4.3 ± 0.2 L/min and HA 2.9 ± 0.2 L/min) consumed 145 g (1.8 g/min) of glucose while performing 80-min of metabolically-matched (SL: 1.66 ± 0.14 V̇O2 L/min 329 ± 28 kcal, HA: 1.59 ± 0.10 V̇O2 L/min, 320 ± 19 kcal) treadmill exercise in SL (757 mmHg) and HA (460 mmHg) conditions after a 5-h exposure. Substrate oxidation rates (g/min) and glucose turnover (mg/kg/min) during exercise were determined using indirect calorimetry and dual tracer technique (13C-glucose oral ingestion and [6,6-2H2]-glucose primed, continuous infusion). RESULTS Total carbohydrate oxidation was higher (P < 0.05) at HA (2.15 ± 0.32) compared to SL (1.39 ± 0.14). Exogenous glucose oxidation rate was lower (P < 0.05) at HA (0.35 ± 0.07) than SL (0.44 ± 0.05). Muscle glycogen oxidation was higher at HA (1.67 ± 0.26) compared to SL (0.83 ± 0.13). Total glucose Ra was lower (P < 0.05) at HA (12.3 ± 1.5) compared to SL (13.8 ± 2.0). Exogenous glucose Ra was lower (P < 0.05) at HA (8.9 ± 1.3) compared to SL (10.9 ± 2.2). Glucose Rd was lower (P < 0.05) at HA (12.7 ± 1.7) compared to SL (14.3 ± 2.0). MCR was lower (P < 0.05) at HA (9.0 ± 1.8) compared to SL (12.1 ± 2.3). Circulating glucose and insulin concentrations were higher in response carbohydrate intake during exercise at HA compared to SL. CONCLUSION Novel results from this investigation suggest that reductions in exogenous carbohydrate oxidation at HA may be multifactorial; however, the apparent insensitivity of peripheral tissue to glucose uptake may be a primary determinate.
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Affiliation(s)
- Lee M Margolis
- U.S. Army Research Institute of Environmental Medicine, Natick, MA, United States of America.
| | - Marques A Wilson
- U.S. Army Research Institute of Environmental Medicine, Natick, MA, United States of America
| | - Claire C Whitney
- U.S. Army Research Institute of Environmental Medicine, Natick, MA, United States of America
| | - Christopher T Carrigan
- U.S. Army Research Institute of Environmental Medicine, Natick, MA, United States of America
| | - Nancy E Murphy
- U.S. Army Research Institute of Environmental Medicine, Natick, MA, United States of America
| | - Patrick N Radcliffe
- U.S. Army Research Institute of Environmental Medicine, Natick, MA, United States of America; Oak Ridge Institute of Science and Education, Oak Ridge, TN, United States of America
| | - Jess A Gwin
- U.S. Army Research Institute of Environmental Medicine, Natick, MA, United States of America; Oak Ridge Institute of Science and Education, Oak Ridge, TN, United States of America
| | - David D Church
- Department of Geriatrics, Center for Translational Research in Aging and Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, AR, United States of America
| | - Robert R Wolfe
- Department of Geriatrics, Center for Translational Research in Aging and Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, AR, United States of America
| | - Arny A Ferrando
- Department of Geriatrics, Center for Translational Research in Aging and Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, AR, United States of America
| | - Andrew J Young
- U.S. Army Research Institute of Environmental Medicine, Natick, MA, United States of America; Oak Ridge Institute of Science and Education, Oak Ridge, TN, United States of America
| | - Stefan M Pasiakos
- U.S. Army Research Institute of Environmental Medicine, Natick, MA, United States of America
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Effects of carbohydrate supplementation on aerobic exercise performance during acute high altitude exposure and after 22 days of acclimatization and energy deficit. J Int Soc Sports Nutr 2020; 17:4. [PMID: 31918720 PMCID: PMC6953153 DOI: 10.1186/s12970-020-0335-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 01/03/2020] [Indexed: 11/18/2022] Open
Abstract
Background The ergogenic effects of supplemental carbohydrate on aerobic exercise performance at high altitude (HA) may be modulated by acclimatization status. Longitudinal evaluation of potential performance benefits of carbohydrate supplementation in the same volunteers before and after acclimatization to HA have not been reported. Purpose This study examined how consuming carbohydrate affected 2-mile time trial performance in lowlanders at HA (4300 m) before and after acclimatization. Methods Fourteen unacclimatized men performed 80 min of metabolically-matched (~ 1.7 L/min) treadmill walking at sea level (SL), after ~ 5 h of acute HA exposure, and after 22 days of HA acclimatization and concomitant 40% energy deficit (chronic HA). Before, and every 20 min during walking, participants consumed either carbohydrate (CHO, n = 8; 65.25 g fructose + 79.75 g glucose, 1.8 g carbohydrate/min) or flavor-matched placebo (PLA, n = 6) beverages. A self-paced 2-mile treadmill time trial was performed immediately after completing the 80-min walk. Results There were no differences (P > 0.05) in time trial duration between CHO and PLA at SL, acute HA, or chronic HA. Time trial duration was longer (P < 0.05) at acute HA (mean ± SD; 27.3 ± 6.3 min) compared to chronic HA (23.6 ± 4.5 min) and SL (17.6 ± 3.6 min); however, time trial duration at chronic HA was still longer than SL (P < 0.05). Conclusion These data suggest that carbohydrate supplementation does not enhance aerobic exercise performance in lowlanders acutely exposed or acclimatized to HA. Trial registration NCT, NCT02731066, Registered March 292,016
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Michalek-Zrabkowska M, Wieckiewicz M, Smardz J, Gac P, Poreba R, Wojakowska A, Mazur G, Martynowicz H. Determination of Inflammatory Markers, Hormonal Disturbances, and Sleepiness Associated with Sleep Bruxism Among Adults. Nat Sci Sleep 2020; 12:969-979. [PMID: 33204200 PMCID: PMC7667147 DOI: 10.2147/nss.s268470] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 09/14/2020] [Indexed: 12/15/2022] Open
Abstract
PURPOSE Sleep bruxism (SB) is characterized by repetitive phasic, tonic, or mixed masticatory muscle activity during sleep with multifactorial etiology. Previous studies have shown that the complex origin of SB can be related to the psychological features of the affected individual, consumption of caffeine and alcohol, smoking, obstructive sleep apnea, diabetes, increased body mass index, hypertension, thyroid diseases, and probable genetic vulnerability. This study aimed to investigate the inflammatory markers, hormonal disturbances, and sleepiness associated with SB, which have a potential effect on the total cardiovascular (CV) risk among relatively young and healthy patients. PATIENTS AND METHODS A total of 74 individuals with probable SB were subjected to single-night polysomnography, followed by blood panel and 24-h urinary excretion tests. The level of daytime sleepiness was assessed in the participants using the Epworth Sleepiness Scale. RESULTS SB was found in 78.4% of participants. The bruxism episode index (BEI) positively correlated with the concentrations of 17-hydroxycorticosteroids, C-reactive protein, and fibrinogen in the collected urine samples. A positive correlation was also found between phasic BEI and glucose concentration 2 h after the consumption of glucose solution. Sleep bruxers showed significantly increased sleepiness compared to nonbruxers (p = 0.02). The scores on sleepiness were positively correlated with mixed BEI, minimal oxygen saturation, and mean heart rate. CONCLUSION The results of this study revealed that participants with SB had metabolic and hormonal disturbances, probably due to stress and sympathetic activity. Moreover, it was found that young sleep bruxers potentially have a high CV risk due to the increased level of inflammatory and stress markers.
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Affiliation(s)
- Monika Michalek-Zrabkowska
- Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw 50-556, Poland
| | - Mieszko Wieckiewicz
- Department of Experimental Dentistry, Wroclaw Medical University, Wroclaw 50-425, Poland
| | - Joanna Smardz
- Department of Experimental Dentistry, Wroclaw Medical University, Wroclaw 50-425, Poland
| | - Pawel Gac
- Department of Hygiene, Wroclaw Medical University, Wroclaw 50-345, Poland
| | - Rafal Poreba
- Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw 50-556, Poland
| | - Anna Wojakowska
- Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw 50-556, Poland
| | - Grzegorz Mazur
- Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw 50-556, Poland
| | - Helena Martynowicz
- Department of Internal Medicine, Occupational Diseases, Hypertension and Clinical Oncology, Wroclaw Medical University, Wroclaw 50-556, Poland
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Barclay RD, Beals JW, Drnevich J, Imai BS, Yau PM, Ulanov AV, Tillin NA, Villegas-Montes M, Paluska SA, Watt PW, De Lisio M, Burd NA, Mackenzie RW. Ingestion of lean meat elevates muscle inositol hexakisphosphate kinase 1 protein content independent of a distinct post-prandial circulating proteome in young adults with obesity. Metabolism 2020; 102:153996. [PMID: 31678069 PMCID: PMC7268923 DOI: 10.1016/j.metabol.2019.153996] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 09/25/2019] [Accepted: 10/06/2019] [Indexed: 01/05/2023]
Abstract
BACKGROUND We have recently shown that a novel signalling kinase, inositol hexakisphosphate kinase 1 (IP6K1), is implicated in whole-body insulin resistance via its inhibitory action on Akt. Insulin and insulin like growth factor 1 (IGF-1) share many intracellular processes with both known to play a key role in glucose and protein metabolism in skeletal muscle. AIMS We aimed to compare IGF/IP6K1/Akt signalling and the plasma proteomic signature in individuals with a range of BMIs after ingestion of lean meat. METHODS Ten lean [Body mass index (BMI) (in kg/m2): 22.7 ± 0.4; Homeostatic model assessment of insulin resistance (HOMAIR): 1.36 ± 0.17], 10 overweight (BMI: 27.1 ± 0.5; HOMAIR: 1.25 ± 0.11), and 10 obese (BMI: 35.9 ± 1.3; HOMAIR: 5.82 ± 0.81) adults received primed continuous L-[ring-13C6]phenylalanine infusions. Blood and muscle biopsy samples were collected at 0 min (post-absorptive), 120 min and 300 min relative to the ingestion of 170 g pork loin (36 g protein and 5 g fat) to examine skeletal muscle protein signalling, plasma proteomic signatures, and whole-body phenylalanine disappearance rates (Rd). RESULTS Phenylalanine Rd was not different in obese compared to lean individuals at all time points and was not responsive to a pork ingestion (basal, P = 0.056; 120 & 300 min, P > 0.05). IP6K1 was elevated in obese individuals at 120 min post-prandial vs basal (P < 0.05). There were no acute differences plasma proteomic profiles between groups in the post-prandial state (P > 0.05). CONCLUSIONS These data demonstrate, for the first time that muscle IP6K1 protein content is elevated after lean meat ingestion in obese adults, suggesting that IP6K1 may be contributing to the dysregulation of nutrient uptake in skeletal muscle. In addition, proteomic analysis showed no differences in proteomic signatures between obese, overweight or lean individuals.
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Affiliation(s)
- Richie D Barclay
- Department of Life Sciences, University of Roehampton, London, UK
| | - Joseph W Beals
- Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States
| | - Jenny Drnevich
- High-Performance Biological Computing, Roy J. Carver Biotechnology Center, University of Illinois, Urbana, IL, United States
| | - Brian S Imai
- Protein Sciences Facility, Roy J. Carver Biotechnology Center, University of Illinois, Urbana, IL, United States
| | - Peter M Yau
- Metabolomics Facility, Roy J. Carver Biotechnology Center, University of Illinois, Urbana, IL, United States
| | - Alexander V Ulanov
- Department of Kinesiology and Community Health, University of Illinois, Urbana, IL, United States
| | - Neale A Tillin
- Department of Life Sciences, University of Roehampton, London, UK
| | | | - Scott A Paluska
- Department of Family Medicine, University of Illinois, Urbana, IL, United States
| | - Peter W Watt
- University of Brighton, Welkin Laboratories, Eastbourne, UK
| | - Michael De Lisio
- School of Human Kinetics, Brain and Mind Institute, Center on Neuromuscular Disease, Regenerative Medicine Program, University of Ottawa, Ottawa, ON, Canada
| | - Nicholas A Burd
- Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States; Department of Kinesiology and Community Health, University of Illinois, Urbana, IL, United States
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Bottura RM, Lima GHO, Hipolide DC, Pesquero JB. Association between ACTN3 and acute mountain sickness. Genes Environ 2019; 41:18. [PMID: 31867082 PMCID: PMC6902444 DOI: 10.1186/s41021-019-0133-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 10/10/2019] [Indexed: 12/17/2022] Open
Abstract
Background During the process of acclimatization, when our organism needs to adjust several metabolic processes in the attempt of establishing a better oxygenation, it is normal that individuals present some symptoms that can lead to the disease of the mountain. However, not everyone presents such symptoms and individuals native of high altitudes regions present genetic differences compared to natives of low altitudes which can generate a better acute adaptation. One of these differences is the higher proportion of type I muscle fibers, which may originate from the R577X polymorphism of the ACTN3 gene. The aim of this study was to compare the response of individuals with different ACTN3 genotypes at simulated 4500 m altitude on the presence of Acute Mountain Sickness (AMS) symptoms. Twenty-three volunteers (RR = 7, RX = 8, XX = 8) spent 4 hours exposed to a simulated altitude of 4500 m inside a normobaric hypoxia chamber. Lactate and glucose concentrations, SpO2, heart rate and the symptoms of AMS were analyzed immediately before entering the chamber and at each hour of exposure. Statistical analysis was performed using IBM SPSS Statistics 21 software. Results Our results point to an association between AMS symptoms and the presence of R allele from R577X polymorphism. Conclusion We conclude that individuals with at least one R allele of the R577X polymorphism seems to be more susceptible to the effects of hypoxia during the acclimatization process and may develop AMS symptoms.
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Affiliation(s)
- Ricardo Muller Bottura
- 1Department of Psychobiology, UNIFESP, Botucatu Street, 862, First Floor, Vila Clementino, SP, ZIP, São Paulo, 04023062 Brazil
| | | | - Debora Cristina Hipolide
- 1Department of Psychobiology, UNIFESP, Botucatu Street, 862, First Floor, Vila Clementino, SP, ZIP, São Paulo, 04023062 Brazil
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Sanz-Quinto S, Moya-Ramón M, Brizuela G, Rice I, Urbán T, López-Grueso R. Nutritional strategies in an elite wheelchair marathoner at 3900 m altitude: a case report. J Int Soc Sports Nutr 2019; 16:51. [PMID: 31707995 PMCID: PMC6842507 DOI: 10.1186/s12970-019-0321-8] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Accepted: 10/31/2019] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Altitude training is a common practice among middle-distance and marathon runners. During acclimatization, sympathetic drive may increase resting metabolic rate (RMR), therefore implementation of targeted nutritional interventions based on training demands and environmental conditions becomes paramount. This single case study represents the first nutritional intervention performed under hypobaric hypoxic conditions (3900 m) in Paralympic sport. These results may elucidate the unique nutritional requirements of upper body endurance athletes training at altitude. CASE PRESENTATION This case study examined the effects of a nutritional intervention on the body mass of a 36-year-old professional wheelchair athlete (silver medalist at the Paralympic Games and 106 victories in assorted road events) during a five-week altitude training camp, divided into pre-altitude at sea level (BN), acclimatization to altitude (Puno, 3860 m) (BH), specific training (W1,2,3,4) and return to sea level (Post) phases. Energy intake (kcal) and body mass (kg) were recorded daily. Results demonstrated significant decrease in body mass between BN and BH (52.6 ± 0.4 vs 50.7 ± 0.5 kg, P < 0.001) which returned to pre-altitude values, upon returning to sea level at Post (52.1 ± 0.5 kg). A greater daily intake was observed during BH (2899 ± 670 kcal) and W1,2,3 (3037 ± 490; 3116 ± 170; 3101 ± 385 kcal) compared to BN (2397 ± 242 kcal, P < 0.01) and Post (2411 ± 137 kcal, P < 0.01). No differences were reported between W4 (2786 ± 375 kcal), BN and Post. The amount of carbohydrates ingested (g · kg- 1) was greater in W1,2,3, (9.6 ± 2.1; 9.9 ± 1.2; 9.6 ± 1.2) than in BN (7.1 ± 1.2) and Post (6.3 ± 0.8, P < 0.001). Effect sizes (Cohen's d) for all variables relative to BN (all time points) exceed a large effect (d > 0.80). CONCLUSIONS These results suggest an elite wheelchair marathoner training at 3860 m required increased nutrient requirements as well as the systematic control needed to re-adapt a nutritional program. Moreover, our findings highlight training and nutritional prescription optimization of elite wheelchair athletes, under challenging environmental conditions.
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Affiliation(s)
- Santiago Sanz-Quinto
- Department of Sport Sciences, Miguel Hernandez University, Elche, Av. de la Universidad s/n, 03202, Elche, Alicante, Spain
| | - Manuel Moya-Ramón
- Department of Sport Sciences, Miguel Hernandez University, Elche, Av. de la Universidad s/n, 03202, Elche, Alicante, Spain.,Department of Sport Sciences, Miguel Hernandez University, Elche, Institute for Health and Biomedical Reaearch (ISABIAL-FISABIO), 03010, Alicante, Spain
| | - Gabriel Brizuela
- Department of Physical Education and Sports, University of Valencia, Gasco Oliag, 3, 46010, Valencia, Spain
| | - Ian Rice
- Department of Kinesiology and Community Health College of Applied Health Sciences, University of Illinois at Urbana-Champaign 2003 Huff Hall, M/C 586, 1206 S. Fourth St, Champaign, IL, 61820, USA
| | - Tomás Urbán
- Department of Sport Sciences, Miguel Hernandez University, Elche, Av. de la Universidad s/n, 03202, Elche, Alicante, Spain
| | - Raúl López-Grueso
- Department of Sport Sciences, Miguel Hernandez University, Elche, Av. de la Universidad s/n, 03202, Elche, Alicante, Spain.
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Moraga FA, Osorio J, Jiménez D, Calderón-Jofré R, Moraga D. Aerobic Capacity, Lactate Concentration, and Work Assessment During Maximum Exercise at Sea Level and High Altitude in Miners Exposed to Chronic Intermittent Hypobaric Hypoxia (3,800 m). Front Physiol 2019; 10:1149. [PMID: 31555155 PMCID: PMC6742696 DOI: 10.3389/fphys.2019.01149] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 08/26/2019] [Indexed: 12/01/2022] Open
Abstract
We previously showed that arterial oxygen content during maximum exercise remains constant at high altitude (HA) in miners exposed to chronic intermittent hypobaric hypoxia (CIHH). Nevertheless, information about VO2, lactate concentration [Lac], and work efficiency are absent in this CIHH miner population. Our aim was to determine aerobic capacity, [Lac], and work efficiency at sea level (SL) and HA during maximum exercise in miners acclimatized to CIHH at 3,800 m. Eight volunteer miners acclimatized to CIHH at HA (> 4 years) performed an exercise test at SL and HA. The test was performed on the 4th day at HA or SL and consisted of three phases: Rest (5 min); Exercise test, where the load was increased by 50 W every 3 min until exhaustion; and a Recovery period of 30 min. During the procedure VO2, transcutaneous arterial saturation (SpO2, %), and HR (bpm) were assessed at each step by a pulse oximeter and venous blood samples were taken to measure [Lac] and hemoglobin concentration. No differences in VO2 and [Lac] in SL vs. HA were observed in this CIHH miner population. By contrast, a higher HR and lower SpO2 were observed at SL compared with HA. During maximum exercise, a reduction in VO2 and [Lac] was observed without differences in intensity (W) and HR. A decrease in [Lac] was observed at maximum effort (250 W) and recovery at HA vs. SL. These findings are related to an increased work efficiency assessment such as gross and net efficiency. This study is the first to show that miners exposed to CIHH maintain their work capacity (intensity) with a fall in oxygen consumption and a decrease in plasmatic lactate concentration at maximal effort at HA. These findings indicate that work efficiency at HA is enhanced.
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Affiliation(s)
- Fernando A Moraga
- Laboratorio de Fisiología, Hipoxia y Función Vascular, Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo, Chile
| | - Jorge Osorio
- Instituto de Estudios de la Salud, Universidad Arturo Prat, Iquique, Chile
| | - Daniel Jiménez
- Escuela de Salud Pública, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Rodrigo Calderón-Jofré
- Laboratorio de Fisiología, Hipoxia y Función Vascular, Departamento de Ciencias Biomédicas, Facultad de Medicina, Universidad Católica del Norte, Coquimbo, Chile.,Departamento de Ciencias Básicas, Universidad Santo Tomás, La Serena, Chile
| | - Daniel Moraga
- Carrera de Medicina, Facultad de Ciencias de la Salud, Universidad de Tarapacá, Arica, Chile
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Bhandari S, Cavalleri GL. Population History and Altitude-Related Adaptation in the Sherpa. Front Physiol 2019; 10:1116. [PMID: 31555147 PMCID: PMC6722185 DOI: 10.3389/fphys.2019.01116] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Accepted: 08/12/2019] [Indexed: 12/29/2022] Open
Abstract
The first ascent of Mount Everest by Tenzing Norgay and Sir Edmund Hillary in 1953 brought global attention to the Sherpa people and human performance at altitude. The Sherpa inhabit the Khumbu Valley of Nepal, and are descendants of a population that has resided continuously on the Tibetan plateau for the past ∼25,000 to 40,000 years. The long exposure of the Sherpa to an inhospitable environment has driven genetic selection and produced distinct adaptive phenotypes. This review summarizes the population history of the Sherpa and their physiological and genetic adaptation to hypoxia. Genomic studies have identified robust signals of positive selection across EPAS1, EGLN1, and PPARA, that are associated with hemoglobin levels, which likely protect the Sherpa from altitude sickness. However, the biological underpinnings of other adaptive phenotypes such as birth weight and the increased reproductive success of Sherpa women are unknown. Further studies are required to identify additional signatures of selection and refine existing Sherpa-specific adaptive phenotypes to understand how genetic factors have underpinned adaptation in this population. By correlating known and emerging signals of genetic selection with adaptive phenotypes, we can further reveal hypoxia-related biological mechanisms of adaptation. Ultimately this work could provide valuable information regarding treatments of hypoxia-related illnesses including stroke, heart failure, lung disease and cancer.
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Affiliation(s)
- Sushil Bhandari
- Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Gianpiero L Cavalleri
- Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
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39
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Two weeks of moderate hypoxia improves glucose tolerance in individuals with type 2 diabetes. Int J Obes (Lond) 2019; 44:744-747. [PMID: 31324880 DOI: 10.1038/s41366-019-0422-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Revised: 06/05/2019] [Accepted: 06/17/2019] [Indexed: 12/31/2022]
Abstract
We previously showed that nightly exposure to moderate hypoxia reduces fasting glucose levels and improves both whole-body skeletal muscle and hepatic insulin sensitivity in individuals with obesity. The goal of this study was to extend this observation in an "at home" setting and determine if nightly exposure to moderate hypoxia improves glucose tolerance in individuals with type 2 diabetes. Eight adults, ages 20-65 years with type 2 diabetes enrolled in our study and slept for 14 consecutive nights at home in a hypoxic tent maintained at 15% O2 (~2400 m). The primary endpoint was insulin sensitivity (Matsuda Index) calculated from a 75-g oral glucose tolerance test. Secondary endpoints included calculations of insulin secretion and beta-cell function, including the area-under-the-curve (AUC) for glucose and insulin, the Insulinogenic Index, and the Disposition Index. We observed the Matsuda Index trended towards a 29% increase following 14 nights of moderate hypoxia (from 1.7 ± 0.7 to 2.2 ± 1.7; p = 0.06). Two-hour glucose AUC was significantly reduced from 501 ± 99 to 439 ± 65 mg/dL × h (p = 0.01). We conclude that 14 nights of moderate hypoxia improves glucose tolerance in individuals with type 2 diabetes. Future studies should confirm whether exposure to moderate hypoxia consistently improves glucose homeostasis in larger sample sizes.
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40
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Sousa Fialho MDL, Abd Jamil AH, Stannard GA, Heather LC. Hypoxia-inducible factor 1 signalling, metabolism and its therapeutic potential in cardiovascular disease. Biochim Biophys Acta Mol Basis Dis 2019; 1865:831-843. [DOI: 10.1016/j.bbadis.2018.09.024] [Citation(s) in RCA: 42] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 08/24/2018] [Accepted: 09/18/2018] [Indexed: 12/20/2022]
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Griffiths A, Shannon OM, Matu J, King R, Deighton K, O'Hara JP. The effects of environmental hypoxia on substrate utilisation during exercise: a meta-analysis. J Int Soc Sports Nutr 2019; 16:10. [PMID: 30813949 PMCID: PMC6391781 DOI: 10.1186/s12970-019-0277-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2018] [Accepted: 02/13/2019] [Indexed: 02/08/2023] Open
Abstract
Background A better understanding of hypoxia-induced changes in substrate utilisation can facilitate the development of nutritional strategies for mountaineers, military personnel and athletes during exposure to altitude. However, reported metabolic responses are currently divergent. As such, this systematic review and meta-analysis aims to determine the changes in substrate utilisation during exercise in hypoxia compared with normoxia and identify study characteristics responsible for the heterogeneity in findings. Methods A total of six databases (PubMed, the Cochrane Library, MEDLINE, SPORTDiscus, PsychINFO, and CINAHL via EBSCOhost) were searched for published original studies, conference proceedings, abstracts, dissertations and theses. Studies were included if they evaluated respiratory exchange ratio (RER) and/or carbohydrate or fat oxidation during steady state exercise matched for relative intensities in normoxia and hypoxia (normobaric or hypobaric). A random-effects meta-analysis was performed on outcome variables. Meta-regression analysis was performed to investigate potential sources of heterogeneity. Results In total, 18 studies were included in the meta-analysis. There was no significant change in RER during exercise matched for relative exercise intensities in hypoxia, compared with normoxia (mean difference: 0.01, 95% CI: -0.02 to 0.05; n = 31, p = 0.45). Meta-regression analysis suggests that consumption of a pre-exercise meal (p < 0.01) and a higher exercise intensity (p = 0.04) when exposed to hypoxia may increase carbohydrate oxidation compared with normoxia. Conclusions Exposure to hypoxia did not induce a consistent change in the relative contribution of carbohydrate or fat to the total energy yield during exercise matched for relative intensities, compared with normoxia. The direction of these responses appears to be mediated by the consumption of a pre-exercise meal and exercise intensity. Electronic supplementary material The online version of this article (10.1186/s12970-019-0277-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Alex Griffiths
- Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, LS6 3QS, UK.
| | - Oliver M Shannon
- Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, LS6 3QS, UK.,Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, Leech Building, Framlington Place, Newcastle Upon Tyne, NE2 4HH, UK
| | - Jamie Matu
- Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, LS6 3QS, UK.,Leeds Institute of Rheumatic and Musculoskeletal Medicine, 2nd floor Chapel Allerton Hospital, Chapeltown Road, Leeds, LS7 4SA, UK
| | - Roderick King
- Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, LS6 3QS, UK
| | - Kevin Deighton
- Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, LS6 3QS, UK
| | - John P O'Hara
- Institute for Sport, Physical Activity and Leisure, Leeds Beckett University, Leeds, LS6 3QS, UK
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Human Genetic Adaptation to High Altitude: Evidence from the Andes. Genes (Basel) 2019; 10:genes10020150. [PMID: 30781443 PMCID: PMC6410003 DOI: 10.3390/genes10020150] [Citation(s) in RCA: 75] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 01/29/2019] [Accepted: 02/11/2019] [Indexed: 12/31/2022] Open
Abstract
Whether Andean populations are genetically adapted to high altitudes has long been of interest. Initial studies focused on physiological changes in the O₂ transport system that occur with acclimatization in newcomers and their comparison with those of long-resident Andeans. These as well as more recent studies indicate that Andeans have somewhat larger lung volumes, narrower alveolar to arterial O₂ gradients, slightly less hypoxic pulmonary vasoconstrictor response, greater uterine artery blood flow during pregnancy, and increased cardiac O2 utilization, which overall suggests greater efficiency of O₂ transfer and utilization. More recent single nucleotide polymorphism and whole-genome sequencing studies indicate that multiple gene regions have undergone recent positive selection in Andeans. These include genes involved in the regulation of vascular control, metabolic hemostasis, and erythropoiesis. However, fundamental questions remain regarding the functional links between these adaptive genomic signals and the unique physiological attributes of highland Andeans. Well-designed physiological and genome association studies are needed to address such questions. It will be especially important to incorporate the role of epigenetic processes (i.e.; non-sequence-based features of the genome) that are vital for transcriptional responses to hypoxia and are potentially heritable across generations. In short, further exploration of the interaction among genetic, epigenetic, and environmental factors in shaping patterns of adaptation to high altitude promises to improve the understanding of the mechanisms underlying human adaptive potential and clarify its implications for human health.
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Caris AV, Santos RVT. Performance and altitude: Ways that nutrition can help. Nutrition 2018; 60:35-40. [PMID: 30529882 DOI: 10.1016/j.nut.2018.09.030] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Accepted: 09/29/2018] [Indexed: 12/18/2022]
Abstract
High altitudes are a challenge for human physiology and for sports enthusiasts. Several reasons lead to deterioration in performance at high altitudes. Hypoxia owing to high altitude causes a breakdown of homeostasis with imbalance in several physiological systems, including the immune system. The reduction in mucosal immunity and inflammation and the predominance of the humoral immune response causes a condition of immunosuppression and an increased likelihood of infection. In addition, it is known that worsening of the immune response is associated with reduced performance. On the other hand, immunonutrition plays an important role in modulating the effects of physical exercise on the immune system. However, to our knowledge, few studies have evaluated the effect of nutrition on the immune system after exercise in hypoxia. Although the association between exercise and hypoxia has been shown to be more severe for the body owing to the sum of stressful agents, supplementation with carbohydrates and glutamine seems to play a relevant role in mitigating immunosuppressive effects. These findings, although limited by the fact that they are the result of very few studies, shed light on a relevant theme for sports physiology and nutrition and suggest that both supplements may be useful for athletes, visitors, and workers in high-altitude regions. The aim of this review was to discuss the effects of high-altitude hypoxia on the human body from the point of view of exercise immunology because it is known that transient immunosuppression after strenuous exercise and competition should be followed by reduction in training overload and worse performance.
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Affiliation(s)
- Aline V Caris
- Department of Psychobiology, Universidade Federal de São Paulo, São Paulo, Brazil
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Suzuki TA, Martins FM, Nachman MW. Altitudinal variation of the gut microbiota in wild house mice. Mol Ecol 2018; 28:2378-2390. [PMID: 30346069 DOI: 10.1111/mec.14905] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Revised: 08/25/2018] [Accepted: 10/06/2018] [Indexed: 12/11/2022]
Abstract
The maintenance of oxygen homeostasis in the gut is critical for the maintenance of a healthy gut microbiota. However, few studies have explored how the concentration of atmospheric oxygen affects the gut microbiota in natural populations. High-altitude environments provide an opportunity to study the potential effects of atmospheric oxygen on the composition and function of the gut microbiota. Here, we characterized the caecal microbial communities of wild house mice (Mus musculus domesticus) in two independent altitudinal transects, one in Ecuador and one in Bolivia, from sea level to nearly 4,000 m. First, we found that differences in altitude were associated with differences in the gut microbial community after controlling for the effects of body mass, diet, reproductive status and population of origin. Second, obligate anaerobes tended to show a positive correlation with altitude, while all other microbes tended to show a negative correlation with altitude. These patterns were seen independently in both transects, consistent with the expected effects of atmospheric oxygen on gut microbes. Prevotella was the most-enriched genus at high elevations in both transects, consistent with observations in high-altitude populations of pikas, ruminants and humans, and also consistent with observations of laboratory mice exposed to hypoxic conditions. Lastly, the renin-angiotensin system, a recently proposed microbiota-mediated pathway of blood pressure regulation, was the top predicted metagenomic pathway enriched in high altitudes in both transects. These results suggest that high-altitude environments affect the composition and function of the gut microbiota in wild mammals.
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Affiliation(s)
- Taichi A Suzuki
- Department of Integrative Biology and Museum of Vertebrate Zoology, University of California Berkeley, Berkeley, California
| | - Felipe M Martins
- Department of Ecology and Evolution, Research School of Biology, The Australian National University, Acton, Australian Capital Territory, Australia
| | - Michael W Nachman
- Department of Integrative Biology and Museum of Vertebrate Zoology, University of California Berkeley, Berkeley, California
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45
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DE Groote E, Britto FA, Bullock L, François M, DE Buck C, Nielens H, Deldicque L. Hypoxic Training Improves Normoxic Glucose Tolerance in Adolescents with Obesity. Med Sci Sports Exerc 2018; 50:2200-2208. [PMID: 29923910 DOI: 10.1249/mss.0000000000001694] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
PURPOSE This study aimed to test whether environmental hypoxia could potentiate the effects of exercise training on glucose metabolism and insulin sensitivity. METHODS Fourteen adolescents with obesity were assigned to 6 wk of exercise training either in normoxic or in hypoxic conditions (FiO2 15%). Adolescents trained three times per week for 50-60 min, including endurance and resistance exercises. Oral glucose tolerance test, blood and morphological analyses, and physical performance tests were performed before and after the training period. RESULTS After training, hypoxia, but not normoxia, decreased the area under the curve of plasma insulin (-49%; P = 0.001) and glucose levels (-14%; P = 0.005) during oral glucose tolerance test. Decreased plasma triglycerides levels (P = 0.03) and increased maximal aerobic power (P = 0.002), work capacity at 160 bpm (P = 0.002), and carbohydrate consumption during exercise (P = 0.03) were measured only in the hypoxic group. CONCLUSIONS Hypoxic exercise training was particularly efficient at improving glucose tolerance and insulin response to a glucose challenge in adolescents with obesity. These results suggest that exercise training in hypoxia could be an interesting strategy against insulin resistance and type 2 diabetes development in adolescents with obesity.
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Affiliation(s)
- Estelle DE Groote
- Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve, BELGIUM
| | - Florian A Britto
- Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve, BELGIUM
| | - Loïc Bullock
- Centre Médical Pédiatrique Clairs Vallons, Louvain-la-Neuve, BELGIUM
| | - Marie François
- Centre Médical Pédiatrique Clairs Vallons, Louvain-la-Neuve, BELGIUM
| | - Carine DE Buck
- Centre Médical Pédiatrique Clairs Vallons, Louvain-la-Neuve, BELGIUM
| | - Henri Nielens
- Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve, BELGIUM
| | - Louise Deldicque
- Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve, BELGIUM
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Gnimassou O, Fernández-Verdejo R, Brook M, Naslain D, Balan E, Sayda M, Cegielski J, Nielens H, Decottignies A, Demoulin JB, Smith K, Atherton PJ, Francaux M, Deldicque L. Environmental hypoxia favors myoblast differentiation and fast phenotype but blunts activation of protein synthesis after resistance exercise in human skeletal muscle. FASEB J 2018; 32:5272-5284. [PMID: 29672220 DOI: 10.1096/fj.201800049rr] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
We hypothesized that a single session of resistance exercise performed in moderate hypoxic (FiO2: 14%) environmental conditions would potentiate the anabolic response during the recovery period spent in normoxia. Twenty subjects performed a 1-leg knee extension session in normoxic or hypoxic conditions. Muscle biopsies were taken 15 min and 4 h after exercise in the vastus lateralis of the exercised and the nonexercised legs. Blood and saliva samples were taken at regular intervals before, during, and after the exercise session. The muscle fractional-protein synthetic rate was determined by deuterium incorporation into proteins, and the protein-degradation rate was determined by methylhistidine release from skeletal muscle. We found that: 1) hypoxia blunted the activation of protein synthesis after resistance exercise; 2) hypoxia down-regulated the transcriptional program of autophagy; 3) hypoxia regulated the expression of genes involved in glucose metabolism at rest and the genes involved in myoblast differentiation and fusion and in muscle contraction machinery after exercise; and 4) the hypoxia-inducible factor-1α pathway was not activated at the time points studied. Contrary to our hypothesis, environmental hypoxia did not potentiate the short-term anabolic response after resistance exercise, but it initiated transcriptional regulations that could potentially translate into satellite cell incorporation and higher force production in the long term.-Gnimassou, O., Fernández-Verdejo, R., Brook, M., Naslain, D., Balan, E., Sayda, M., Cegielski, J., Nielens, H., Decottignies, A., Demoulin, J.-B., Smith, K., Atherton, P. J., Fancaux, M., Deldicque, L. Environmental hypoxia favors myoblast differentiation and fast phenotype but blunts activation of protein synthesis after resistance exercise in human skeletal muscle.
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Affiliation(s)
- Olouyomi Gnimassou
- Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium
| | - Rodrigo Fernández-Verdejo
- Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium
- Carrera de Nutrición y Dietética, Departamento de Ciencias de la Salud, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Matthew Brook
- Medical Research Council-Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research, Royal Derby Hospital, University of Nottingham, Derby, United Kingdom
- Clinical, Metabolic, and Molecular Physiology, Royal Derby Hospital, University of Nottingham, Derby, United Kingdom
| | - Damien Naslain
- Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium
| | - Estelle Balan
- Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium
| | - Mariwan Sayda
- Medical Research Council-Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research, Royal Derby Hospital, University of Nottingham, Derby, United Kingdom
- Clinical, Metabolic, and Molecular Physiology, Royal Derby Hospital, University of Nottingham, Derby, United Kingdom
| | - Jessica Cegielski
- Medical Research Council-Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research, Royal Derby Hospital, University of Nottingham, Derby, United Kingdom
- Clinical, Metabolic, and Molecular Physiology, Royal Derby Hospital, University of Nottingham, Derby, United Kingdom
| | - Henri Nielens
- Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium
| | | | | | - Kenneth Smith
- Medical Research Council-Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research, Royal Derby Hospital, University of Nottingham, Derby, United Kingdom
- Clinical, Metabolic, and Molecular Physiology, Royal Derby Hospital, University of Nottingham, Derby, United Kingdom
| | - Philip J Atherton
- Medical Research Council-Arthritis Research UK Centre of Excellence for Musculoskeletal Ageing Research, Royal Derby Hospital, University of Nottingham, Derby, United Kingdom
- Clinical, Metabolic, and Molecular Physiology, Royal Derby Hospital, University of Nottingham, Derby, United Kingdom
| | - Marc Francaux
- Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium
| | - Louise Deldicque
- Institute of Neuroscience, Université Catholique de Louvain, Louvain-la-Neuve, Belgium
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47
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McClelland GB, Scott GR. Evolved Mechanisms of Aerobic Performance and Hypoxia Resistance in High-Altitude Natives. Annu Rev Physiol 2018; 81:561-583. [PMID: 30256727 DOI: 10.1146/annurev-physiol-021317-121527] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Comparative physiology studies of high-altitude species provide an exceptional opportunity to understand naturally evolved mechanisms of hypoxia resistance. Aerobic capacity (VO2max) is a critical performance trait under positive selection in some high-altitude taxa, and several high-altitude natives have evolved to resist the depressive effects of hypoxia on VO2max. This is associated with enhanced flux capacity through the O2 transport cascade and attenuation of the maladaptive responses to chronic hypoxia that can impair O2 transport. Some highlanders exhibit elevated rates of carbohydrate oxidation during exercise, taking advantage of its high ATP yield per mole of O2. Certain highland native animals have also evolved more oxidative muscles and can sustain high rates of lipid oxidation to support thermogenesis. The underlying mechanisms include regulatory adjustments of metabolic pathways and to gene expression networks. Therefore, the evolution of hypoxia resistance in high-altitude natives involves integrated functional changes in the pathways for O2 and substrate delivery and utilization by mitochondria.
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Affiliation(s)
- Grant B McClelland
- Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada;
| | - Graham R Scott
- Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada;
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48
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HILL NEILE, DEIGHTON KEVIN, MATU JAMIE, MISRA SHIVANI, OLIVER NICKS, NEWMAN CARRIE, MELLOR ADRIAN, O’HARA JOHN, WOODS DAVID. Continuous Glucose Monitoring at High Altitude—Effects on Glucose Homeostasis. Med Sci Sports Exerc 2018; 50:1679-1686. [DOI: 10.1249/mss.0000000000001624] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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49
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Young AJ, Berryman CE, Kenefick RW, Derosier AN, Margolis LM, Wilson MA, Carrigan CT, Murphy NE, Carbone JW, Rood JC, Pasiakos SM. Altitude Acclimatization Alleviates the Hypoxia-Induced Suppression of Exogenous Glucose Oxidation During Steady-State Aerobic Exercise. Front Physiol 2018; 9:830. [PMID: 30038576 PMCID: PMC6046468 DOI: 10.3389/fphys.2018.00830] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Accepted: 06/12/2018] [Indexed: 12/20/2022] Open
Abstract
This study investigated how high-altitude (HA, 4300 m) acclimatization affected exogenous glucose oxidation during aerobic exercise. Sea-level (SL) residents (n = 14 men) performed 80-min, metabolically matched exercise (V˙O2 ∼ 1.7 L/min) at SL and at HA < 5 h after arrival (acute HA, AHA) and following 22-d of HA acclimatization (chronic HA, CHA). During HA acclimatization, participants sustained a controlled negative energy balance (-40%) to simulate the “real world” conditions that lowlanders typically experience during HA sojourns. During exercise, participants consumed carbohydrate (CHO, n = 8, 65.25 g fructose + 79.75 g glucose, 1.8 g carbohydrate/min) or placebo (PLA, n = 6). Total carbohydrate oxidation was determined by indirect calorimetry and exogenous glucose oxidation by tracer technique with 13C. Participants lost (P ≤ 0.05, mean ± SD) 7.9 ± 1.9 kg body mass during the HA acclimatization and energy deficit period. In CHO, total exogenous glucose oxidized during the final 40 min of exercise was lower (P < 0.01) at AHA (7.4 ± 3.7 g) than SL (15.3 ± 2.2 g) and CHA (12.4 ± 2.3 g), but there were no differences between SL and CHA. Blood glucose and insulin increased (P ≤ 0.05) during the first 20 min of exercise in CHO, but not PLA. In CHO, glucose declined to pre-exercise concentrations as exercise continued at SL, but remained elevated (P ≤ 0.05) throughout exercise at AHA and CHA. Insulin increased during exercise in CHO, but the increase was greater (P ≤ 0.05) at AHA than at SL and CHA, which did not differ. Thus, while acute hypoxia suppressed exogenous glucose oxidation during steady-state aerobic exercise, that hypoxic suppression is alleviated following altitude acclimatization and concomitant negative energy balance.
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Affiliation(s)
- Andrew J Young
- Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, MA, United States.,Oak Ridge Institute of Science and Education, Oak Ridge, TN, United States
| | - Claire E Berryman
- Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, MA, United States.,Oak Ridge Institute of Science and Education, Oak Ridge, TN, United States
| | - Robert W Kenefick
- Thermal Mountain and Medicine Division, United States Army Research Institute of Environmental Medicine, Natick, MA, United States
| | - Allyson N Derosier
- Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, MA, United States.,Oak Ridge Institute of Science and Education, Oak Ridge, TN, United States
| | - Lee M Margolis
- Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, MA, United States.,Oak Ridge Institute of Science and Education, Oak Ridge, TN, United States
| | - Marques A Wilson
- Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, MA, United States
| | - Christopher T Carrigan
- Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, MA, United States
| | - Nancy E Murphy
- Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, MA, United States
| | - John W Carbone
- Oak Ridge Institute of Science and Education, Oak Ridge, TN, United States.,School of Health Sciences, Eastern Michigan University, Ypsilanti, MI, United States
| | - Jennifer C Rood
- Pennington Biomedical Research Center, Baton Rouge, LA, United States
| | - Stefan M Pasiakos
- Military Nutrition Division, United States Army Research Institute of Environmental Medicine, Natick, MA, United States
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50
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Park HY, Kim J, Park MY, Chung N, Hwang H, Nam SS, Lim K. Exposure and Exercise Training in Hypoxic Conditions as a New Obesity Therapeutic Modality: A Mini Review. J Obes Metab Syndr 2018; 27:93-101. [PMID: 31089548 PMCID: PMC6489458 DOI: 10.7570/jomes.2018.27.2.93] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Revised: 05/08/2018] [Accepted: 05/16/2018] [Indexed: 01/15/2023] Open
Abstract
Obesity is an important health problem caused by positive energy balance. Generally, low calorie dietary intake combined with regular exercise is the most common modality to lose bodily fat in obese people. Although this is the first modality of choice for obesity treatment, it needs to be applied to obese patients for at least 12 weeks or more and it does not provide consistent results because it is difficult to suppress increased appetite due to exercise. Recently, many researchers have been applying hypoxic conditions for the treatment of obesity, as many studies show that people residing in high altitudes have a lower percentage of body fat and fewer obesity-related illnesses than people living at sea level. Hypoxic therapy treatment, including hypoxic exposure or hypoxic exercise training, is recommended as a way to treat and prevent obesity by suppression of appetite, increasing basal metabolic rate and fat oxidation, and minimizing side effects. Hypoxic therapy inhibits energy intake and appetite-related hormones, and enhances various cardiovascular and metabolic function parameters. These observations indicate that hypoxic therapy is a new treatment modality for inducing fat reduction and promoting metabolic and cardiovascular health, which may be an important and necessary strategy for the treatment of obesity. As such, hypoxic therapy is now used as a general medical practice for obesity treatment in many developed countries. Therefore, hypoxic therapy could be a new, practical, and useful therapeutic modality for obesity and obesity-related comorbidities.
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Affiliation(s)
- Hun-Young Park
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul, Korea
| | - Jisu Kim
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul, Korea
| | - Mi-Young Park
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul, Korea
| | - Nana Chung
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul, Korea
| | - Hyejung Hwang
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul, Korea
| | - Sang-Seok Nam
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul, Korea
| | - Kiwon Lim
- Physical Activity and Performance Institute (PAPI), Konkuk University, Seoul, Korea.,Laboratory of Exercise Nutrition, Department of Physical Education, Konkuk University, Seoul, Korea
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